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Hyaluronan degradation by HYAL2 is essential for odontoblastic differentiation and migration of mouse dental papilla cells Matrix Biol. (IF 6.9) Pub Date : 2024-03-13 Haiyan Huang, Xiaoyu Hu, Jiayan Wu, Chenyu Song, Zhixin Tian, Beizhan Jiang
The coordination between odontoblastic differentiation and directed cell migration of mesenchymal progenitors is necessary for regular dentin formation. The synthesis and degradation of hyaluronan (HA) in the extracellular matrix create a permissive niche that directly regulates cell behaviors. However, the role and mechanisms of HA degradation in dentin formation remain unknown. In this work, we present
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Macrophage phenotype is determinant for fibrosis development in keloid disease Matrix Biol. (IF 6.9) Pub Date : 2024-03-12 Zélie Dirand, Mélissa Maraux, Marion Tissot, Brice Chatelain, Dorothy Supp, Céline Viennet, Sylvain Perruche, Gwenaël Rolin
Keloid refers to a fibroproliferative disorder characterized by an accumulation of extracellular matrix (ECM) components at the dermis level, overgrowth beyond initial wound, and formation of tumor-like nodule areas. Treating keloid is still an unmet clinical need and the lack of an efficient therapy is clearly related to limited knowledge about keloid etiology, despite the growing interest of the
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The role of fibrosis in cardiomyopathies: An opportunity to develop novel biomarkers of disease activity Matrix Biol. (IF 6.9) Pub Date : 2024-02-28 Elisavet Angeli, Maria Jordan, Mandy Otto, Stevan D. Stojanović, Morten Karsdal, Johann Bauersachs, Thomas Thum, Jan Fiedler, Federica Genovese
Cardiomyopathies encompass a spectrum of heart disorders with diverse causes and presentations. Fibrosis stands out as a shared hallmark among various cardiomyopathies, reflecting a common thread in their pathogenesis. This prevalent fibrotic response is intricately linked to the consequences of dysregulated extracellular matrix (ECM) remodeling, emphasizing its significance in the development and
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The role of positional information in determining dermal fibroblast diversity Matrix Biol. (IF 6.9) Pub Date : 2024-02-28 Pratyusha Chitturi, Andrew Leask
The largest mammalian organ, skin, consisting of a dermal connective tissue layer that underlies and supports the epidermis, acts as a protective barrier that excludes external pathogens and disseminates sensory signals emanating from the local microenvironment. Dermal connective tissue is comprised of a collagen-rich extracellular matrix (ECM) that is produced by connective tissue fibroblasts resident
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Microvascular damage, neuroinflammation and extracellular matrix remodeling in Col18a1 knockout mice as a model for early cerebral small vessel disease Matrix Biol. (IF 6.9) Pub Date : 2024-02-21 Mahsima Khoshneviszadeh, Solveig Henneicke, Daniel Pirici, Akilashree Senthilnathan, Lorena Morton, Philipp Arndt, Rahul Kaushik, Oula Norman, Jari Jukkola, Ildiko Rita Dunay, Constanze Seidenbecher, Anne Heikkinen, Stefanie Schreiber, Alexander Dityatev
Collagen type XVIII (COL18) is an abundant heparan sulfate proteoglycan in vascular basement membranes. Here, we asked (i) if the loss of COL18 would result in blood-brain barrier (BBB) breakdown, pathological alterations of small arteries and capillaries and neuroinflammation as found in cerebral small vessel disease (CSVD) and (ii) if such changes may be associated with remodeling of synapses and
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A lysyl oxidase-responsive collagen peptide illuminates collagen remodeling in wound healing Matrix Biol. (IF 6.9) Pub Date : 2024-02-19 Paul Hiebert, Giuseppe Antoniazzi, Matthew Aronoff, Sabine Werner, Helma Wennemers
Tissue repair and fibrosis involve the dynamic remodeling of collagen, and accurate detection of these sites is of utmost importance. Here, we use a collagen peptide sensor () to visualize collagen formation and remodeling during wound healing in mice and humans. We show that the probe binds selectively to sites of collagen formation and remodeling at different stages of healing. Compared to conventional
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The Adhesion GPCR and PCP component Flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix Matrix Biol. (IF 6.9) Pub Date : 2024-02-18 Johanna Lena Schön, Victoria Elisabeth Groß, Willem Berend Post, Alexandra Daum, Daniel Matúš, Johanna Pilz, Rene Schnorr, Susanne Horn, Miriam Bäumers, Stefanie Weidtkamp-Peters, Samantha Hughes, Torsten Schöneberg, Simone Prömel
The extracellular matrix (ECM) is a network of macromolecules that presents a vital scaffold for cells and enables multiple ways of cellular communication. Thus, it is essential for many physiological processes such as development, tissue morphogenesis, homeostasis, the shape and partially the size of the body and its organs. To ensure these, the composition of the ECM is tissue-specific and highly
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Dysfunctional latent transforming growth factor β activation after corneal injury in a classical Ehlers–Danlos model Matrix Biol. (IF 6.9) Pub Date : 2024-02-09 Mei Sun, Ana Carolina Acosta, Victoria Emerick, Sheila Adams, Marcel Y Avila, Curtis E Margo, Edgar M Espana
Patients with classical Ehlers Danlos syndrome (cEDS) suffer impaired wound healing and from scars formed after injuries that are atrophic and difficult to close surgically. Haploinsufficiency in COL5A1 creates systemic morphological and functional alterations in the entire body. We investigated mechanisms that impair wound healing from corneal lacerations (full thickness injuries) in a mouse model
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Keratinocyte integrin α3β1 induces expression of the macrophage stimulating factor, CSF-1, through a YAP/TEAD-dependent mechanism. Matrix Biol. (IF 6.9) Pub Date : 2024-02-08 Whitney M. Longmate, Emily Norton, Giesse Albeche Duarte, Lei Wu, Mathieu R. DiPersio, John M. Lamar, C. Michael DiPersio
The development of wound therapy targeting integrins is hampered by inadequate understanding of integrin function in cutaneous wound healing and the wound microenvironment. Following cutaneous injury, keratinocytes migrate to restore the skin barrier, and macrophages aid in debris clearance. Thus, both keratinocytes and macrophages are critical to the coordination of tissue repair. Keratinocyte integrins
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Kidney resident macrophages have distinct subsets and multifunctional roles Matrix Biol. (IF 6.9) Pub Date : 2024-02-07 Christine Chew, Oliver J Brand, Tomohiko Yamamura, Craig Lawless, Mychel Raony Paiva Teixeira Morais, Leo Zeef, I-Hsuan Lin, Gareth Howell, Sylvia Lui, Franziska Lausecker, Christopher Jagger, Tovah N Shaw, Siddharth Krishnan, Flora A McClure, Hayley Bridgeman, Kelly Wemyss, Joanne E Konkel, Tracy Hussell, Rachel Lennon
The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages
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Novel muscle-derived extracellular matrix hydrogel promotes angiogenesis and neurogenesis in volumetric muscle loss Matrix Biol. (IF 6.9) Pub Date : 2024-02-06 Zhuoyue Chen, Yaqing Huang, Hao Xing, Tiffany Tseng, Hailey Edelman, Rachel Perry, Themis R. Kyriakides
Volumetric muscle loss (VML) represents a clinical challenge due to the limited regenerative capacity of skeletal muscle. Most often, it results in scar tissue formation and loss of function, which cannot be prevented by current therapies. Decellularized extracellular matrix (DEM) has emerged as a native biomaterial for the enhancement of tissue repair. Here, we report the generation and characterization
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Thrombospondin-1 promotes mechanical stress-mediated ligamentum flavum hypertrophy through the TGFβ1/Smad3 signaling pathway Matrix Biol. (IF 6.9) Pub Date : 2024-01-26 Run Zhao, Jiale Dong, Chunlei Liu, Mingheng Li, Ruiqian Tan, Chengshuo Fei, Yanlin Chen, Xinxing Yang, Jiawei Shi, Jiajia Xu, Liang Wang, Peng Li, Zhongmin Zhang
Lumbar spinal canal stenosis is primarily caused by ligamentum flavum hypertrophy (LFH), which is a significant pathological factor. Nevertheless, the precise molecular basis for the development of LFH remains uncertain. The current investigation observed a notable increase in thrombospondin-1 (THBS1) expression in LFH through proteomics analysis and single-cell RNA-sequencing analysis of clinical
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Inter-alpha-trypsin inhibitor (IαI) and hyaluronan modifications enhance the innate immune response to influenza virus in the lung Matrix Biol. (IF 6.9) Pub Date : 2024-01-15 Fengying Tang, Stephen R. Reeves, Jourdan E. Brune, Mary Y. Chang, Christina K. Chan, Peter Waldron, Sheona P. Drummond, Caroline M. Milner, Kimberly M. Alonge, Stavros Garantziotis, Anthony J. Day, William A. Altemeier, Charles W. Frevert
The inter-alpha-trypsin inhibitor (IαI) complex is composed of the bikunin core protein with a single chondroitin sulfate (CS) attached and one or two heavy chains (HCs) covalently linked to the CS chain. The HCs from IαI can be transferred to hyaluronan (HA) through a TNFα-stimulated gene-6 (TSG-6) dependent process to form an HC•HA matrix. Previous studies reported increased IαI, HA, and HC•HA complexes
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Three-dimensional co-culturing of stem cell-derived cardiomyocytes and cardiac fibroblasts reveals a role for both cell types in Marfan-related cardiomyopathy Matrix Biol. (IF 6.9) Pub Date : 2024-01-13 Jeffrey Aalders, Laurens Léger, Louis Van der Meeren, Sanjay Sinha, Andre G. Skirtach, Julie De Backer, Jolanda van Hengel
Pathogenic variants in the FBN1 gene, which encodes the extracellular matrix protein fibrillin-1, cause Marfan syndrome (MFS), which affects multiple organ systems, including the cardiovascular system. Myocardial dysfunction has been observed in a subset of patients with MFS and in several MFS mouse models. However, there is limited understanding of the intrinsic consequences of FBN1 variants on cardiomyocytes
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S100A4 a classical DAMP as a therapeutic target in fibrosis Matrix Biol. (IF 6.9) Pub Date : 2024-01-12 Steven O'Reilly
Fibrosis regardless of aetiology is characterised by persistently activated myofibroblasts that are contractile and secrete excessive amounts of extracellular matrix molecules that leads to loss of organ function. Damage-Associated Molecular Patterns (DAMPs) are endogenous host-derived molecules that are released from cells dying or under stress that can be triggered by a variety of insults, either
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Dynamic changes in mitral valve extracellular matrix, tissue mechanics and function in a mouse model of Marfan syndrome Matrix Biol. (IF 6.9) Pub Date : 2024-01-06 Brittany A. Gonzalez, Samuel W. Harmeyer, Taejeong Song, Sakthivel Sadayappan, Katherine E. Yutzey
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Inhibiting JAK1, not NF-κB, reverses the effect of pro-inflammatory cytokines on engineered human ligament function Matrix Biol. (IF 6.9) Pub Date : 2023-12-25 Alec M. Avey, Florence Devos, Albany G. Roberts, El Sayed El Essawy, Keith Baar
The role of inflammation in chronic tendon/ligament injury is hotly debated. There is less debate about inflammation following acute injury. To better understand the effect of acute inflammation, in this study we developed a multi-cytokine model of inflammatory tendinitis. The combined treatment with TNF-α, IL-1β, and IL-6, at dosages well below what are routinely used in vitro, decreased the mechanical
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Tissue Transglutaminase 2 has higher affinity for relaxed than for stretched fibronectin fibers Matrix Biol. (IF 6.9) Pub Date : 2023-12-20 Kateryna Selcuk, Alexander Leitner, Lukas Braun, Fanny Le Blanc, Paulina Pacak, Simon Pot, Viola Vogel
Tissue transglutaminase 2 (TG2) plays a vital role in stabilizing extracellular matrix (ECM) proteins through enzymatic crosslinking during tissue growth, repair, and inflammation. TG2 also binds non-covalently to fibronectin (FN), an essential component of the ECM, facilitating cell adhesion, migration, proliferation, and survival. However, the interaction between TG2 and fibrillar FN remains poorly
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A role for decorin in improving motor deficits after traumatic brain injury Matrix Biol. (IF 6.9) Pub Date : 2023-12-21 Kaori Oshima, Noah Siddiqui, James E. Orfila, Danelle Carter, Justin Laing, Xiaorui Han, Igor Zakharevich, Renato V Iozzo, Arsen Ghasabyan, Hunter Moore, Fuming Zhang, Robert J Linhardt, Ernest E Moore, Nidia Quillinan, Eric P Schmidt, Paco S Herson, Joseph A Hippensteel
Traumatic brain injury (TBI) is the leading cause of death and disability due to injury worldwide. Extracellular matrix (ECM) remodeling is known to significantly contribute to TBI pathophysiology. Glycosaminoglycans, which are long-chain, variably sulfated polysaccharides abundant within the ECM, have previously been shown to be substantially altered after TBI. In this study, we sought to delineate
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Identification of Periostin as a critical niche for myofibroblast dynamics and fibrosis during tendon healing Matrix Biol. (IF 6.9) Pub Date : 2023-12-13 Jessica E. Ackerman, Samantha N. Muscat, Emmanuela Adjei-Sowah, Antonion Korcari, Anne E.C. Nichols, Mark R. Buckley, Alayna E. Loiselle
Tendon injuries are a major clinical problem, with poor patient outcomes caused by abundant scar tissue deposition during healing. Myofibroblasts play a critical role in the initial restoration of structural integrity after injury. However, persistent myofibroblast activity drives the transition to fibrotic scar tissue formation. As such, disrupting myofibroblast persistence is a key therapeutic target
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Novel insights into the role of Discoidin domain receptor 2 (DDR2) in cancer progression: a new avenue of therapeutic intervention Matrix Biol. (IF 6.9) Pub Date : 2023-12-09 Paola Trono, Flavia Ottavi, Laura Rosano'
Discoidin domain receptors (DDRs), including DDR1 and DDR2, are a unique class of receptor tyrosine kinases (RTKs) activated by collagens at the cell-matrix boundary interface. The peculiar mode of activation makes DDRs as key cellular sensors of microenvironmental changes, with a critical role in all physiological and pathological processes governed by collagen remodeling. DDRs are widely expressed
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Collagen prolyl 4-hydroxylase isoenzymes I and II have sequence specificity towards different X-Pro-Gly triplets Matrix Biol. (IF 6.9) Pub Date : 2023-12-09 Antti M. Salo, Pekka Rappu, M.Kristian Koski, Emma Karjalainen, Valerio Izzi, Kati Drushinin, Ilkka Miinalainen, Jarmo Käpylä, Jyrki Heino, Johanna Myllyharju
Collagen biosynthesis requires several co- and post-translational modifications of lysine and proline residues to form structurally and functionally competent collagen molecules. Formation of 4-hydroxyproline (4Hyp) in Y-position prolines of the repetitive -X-Y-Gly- sequences provides thermal stability for the triple-helical collagen molecules. 4Hyp formation is catalyzed by a collagen prolyl 4-hydroxylase
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The cochlear matrisome: Importance in hearing and deafness Matrix Biol. (IF 6.9) Pub Date : 2023-12-07 Mary T. Pressé, Brigitte Malgrange, Laurence Delacroix
The extracellular matrix (ECM) consists in a complex meshwork of collagens, glycoproteins, and proteoglycans, which serves a scaffolding function and provides viscoelastic properties to the tissues. ECM acts as a biomechanical support, and actively participates in cell signaling to induce tissular changes in response to environmental forces and soluble cues. Given the remarkable complexity of the inner
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Peroxidasin is required for full viability in development and for maintenance of tissue mechanics in adults Matrix Biol. (IF 6.9) Pub Date : 2023-11-23 K. Elkie Peebles, Kimberly S. LaFever, Patrick S. Page-McCaw, Selene Colon, Dan Wang, Aubrie M. Stricker, Nicholas Ferrell, Gautam Bhave, Andrea Page-McCaw
Basement membranes are thin strong sheets of extracellular matrix. They provide mechanical and biochemical support to epithelia, muscles, nerves, and blood vessels, among other tissues. The mechanical properties of basement membranes are conferred in part by Collagen IV (Col4), an abundant protein of basement membranes that forms an extensive two-dimensional network through head-to-head and tail-to-tail
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Fiber alignment in 3D collagen networks as a biophysical marker for cell contractility Matrix Biol. (IF 6.9) Pub Date : 2023-11-14 David Böhringer, Andreas Bauer, Ivana Moravec, Lars Bischof, Delf Kah, Christoph Mark, Thomas J. Grundy, Ekkehard Görlach, Geraldine M O’Neill, Silvia Budday, Pamela L. Strissel, Reiner Strick, Andrea Malandrino, Richard Gerum, Michael Mak, Martin Rausch, Ben Fabry
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TGF-β induces matrisome pathological alterations and EMT in patient-derived prostate cancer tumoroids Matrix Biol. (IF 6.9) Pub Date : 2023-11-08 Soraia Fernandes, Jorge Oliver-De La Cruz, Sofia Morazzo, Francesco Niro, Marco Cassani, Helena Ďuríková, Alessio Caravella, Piergiuseppe Fiore, Giulia Azzato, Giuseppe De Marco, Agostino Lauria, Valerio Izzi, Veronika Bosáková, Jan Fric, Petr Filipensky, Giancarlo Forte
Extracellular matrix (ECM) tumorigenic alterations resulting in high matrix deposition and stiffening are hallmarks of adenocarcinomas and are collectively defined as desmoplasia. Here, we thoroughly analysed primary prostate cancer tissues obtained from numerous patients undergoing radical prostatectomy to highlight reproducible structural changes in the ECM leading to the loss of the glandular architecture
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Targeting the αVβ3/NgR2 pathway in neuroendocrine prostate cancer Matrix Biol. (IF 6.9) Pub Date : 2023-11-11 Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino
Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically
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Age related changes in hyaluronan expression leads to Meibomian gland dysfunction Matrix Biol. (IF 6.9) Pub Date : 2023-11-08 Sudhir Verma, Isabel Y. Moreno, Mingxia Sun, Tarsis Ferreira Gesteira, Vivien J. Coulson-Thomas
The prevalence of dry eye disease (DED) ranges from ∼5 to 50 % and its associated symptoms decrease productivity and reduce the quality of life. Approximately 85 % of all DED cases are caused by Meibomian gland dysfunction (MGD). As humans and mice age, their Meibomian glands (MGs) undergo age-related changes resulting in age related-MGD (ARMGD). The precise cause of ARMGD remains elusive, which makes
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Pulmonary fibroelastosis - A review Matrix Biol. (IF 6.9) Pub Date : 2023-11-03 Dan J.K. Yombo, Satish K. Madala, Chanukya P. Vemulapalli, Harshavardhana H. Ediga, William D. Hardie
Elastin is a long-lived fibrous protein that is abundant in the extracellular matrix of the lung. Elastic fibers provide the lung the characteristic elasticity during inhalation with recoil during exhalation thereby ensuring efficient gas exchange. Excessive deposition of elastin and other extracellular matrix proteins reduces lung compliance by impairing ventilation and compromising gas exchange.
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Mmp14 is required for matrisome homeostasis and circadian rhythm in fibroblasts Matrix Biol. (IF 6.9) Pub Date : 2023-10-31 Ching-Yan Chloé Yeung, Richa Garva, Adam Pickard, Yinhui Lu, Venkatesh Mallikarjun, Joe Swift, Susan H. Taylor, Jyoti Rai, David R. Eyre, Mayank Chaturvedi, Yoshifumi Itoh, Qing-Jun Meng, Cornelia Mauch, Paola Zigrino, Karl E. Kadler
The circadian clock in tendon regulates the daily rhythmic synthesis of collagen-I and the appearance and disappearance of small-diameter collagen fibrils in the extracellular matrix. How the fibrils are assembled and removed is not fully understood. Here, we first showed that the collagenase, membrane type I-matrix metalloproteinase (MT1-MMP, encoded by Mmp14), is regulated by the circadian clock
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Tissue inhibitors of metalloproteinases are proteolytic targets of matrix metalloproteinase 9 Matrix Biol. (IF 6.9) Pub Date : 2023-10-06 Sasha Coates-Park, Carolyn Lazaroff, Sadeechya Gurung, Josh Rich, Alexandra Colladay, Maura O'Neill, Georgina S. Butler, Christopher M. Overall, William G. Stetler-Stevenson, David Peeney
Extracellular proteolysis and turnover are core processes of tissue homeostasis. The predominant matrix-degrading enzymes are members of the Matrix Metalloproteinase (MMP) family. MMPs extensively degrade core matrix components in addition to processing a range of other factors in the extracellular, plasma membrane, and intracellular compartments. The proteolytic activity of MMPs is modulated by the
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Molecular cues for immune cells from small leucine-rich repeat proteoglycans in their extracellular matrix-associated and free forms Matrix Biol. (IF 6.9) Pub Date : 2023-10-02 George Maiti, Sean Ashworth, Tansol Choi, Shukti Chakravarti
In this review we highlight emerging immune regulatory functions of lumican, keratocan, fibromodulin, biglycan and decorin, which are members of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). These SLRPs have been studied extensively as collagen-fibril regulatory structural components of the skin, cornea, bone and cartilage in homeostasis. However, SLRPs released from
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Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes Matrix Biol. (IF 6.9) Pub Date : 2023-09-30 Nadine Nagy, Gernot Kaber, Vivekananda G. Sunkari, Payton L. Marshall, Aviv Hargil, Hedwich F. Kuipers, Heather D. Ishak, Marika Bogdani, Rebecca L. Hull, Maria Grandoch, Jens W. Fischer, Tracey L. McLaughlin, Thomas N. Wight, Paul L. Bollyky
Pancreatic β-cell dysfunction and death are central to the pathogenesis of type 2 diabetes (T2D). We identified a novel role for the inflammatory extracellular matrix polymer hyaluronan (HA) in this pathophysiology. Low concentrations of HA were present in healthy pancreatic islets. However, HA substantially accumulated in cadaveric islets of T2D patients and islets of the db/db mouse model of T2D
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Unraveling the role of TGFβ signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models Matrix Biol. (IF 6.9) Pub Date : 2023-09-06 Violette Deleeuw, Eric Carlson, Marjolijn Renard, Keith D. Zientek, Phillip A. Wilmarth, Ashok P. Reddy, Elise C. Manalo, Sara F. Tufa, Douglas R. Keene, Margie Olbinado, Marco Stampanoni, Sachiko Kanki, Hiromi Yanagisawa, Laura Muiño Mosquera, Patrick Sips, Julie De Backer, Lynn Y. Sakai
Although abnormal TGFβ signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, its precise role in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to elucidate the role of TGFβ signaling in three Fbn1 mutant mouse models representing a range of aortic
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En route towards a personalized medicine approach: Innovative therapeutic modalities for connective tissue disorders Matrix Biol. (IF 6.9) Pub Date : 2023-08-30 Charlene Redhead, Nandaraj Taye, Dirk Hubmacher
Connective tissue disorders can be caused by pathogenic variants (mutations) in genes encoding extracellular matrix (ECM) proteins. Such disorders typically manifest during development or postnatal growth and result in significant morbidity and mortality. The development of curative treatments for connective tissue disorders is hampered in part by the inability of many mature connective tissues to
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Autocrine IL-6 drives cell and extracellular matrix anisotropy in scar fibroblasts Matrix Biol. (IF 6.9) Pub Date : 2023-09-01 Fiona N. Kenny, Stefania Marcotti, Deandra Belo De Freitas, Elena M. Drudi, Vivienne Leech, Rachel E. Bell, Jennifer Easton, María-del-Carmen Díaz-de-la-Loza, Roland Fleck, Leanne Allison, Christina Philippeos, Angelika Manhart, Tanya J. Shaw, Brian M. Stramer
Fibrosis is associated with dramatic changes in extracellular matrix (ECM) architecture of unknown etiology. Here we exploit keloid scars as a paradigm to understand fibrotic ECM organization. We reveal that keloid patient fibroblasts uniquely produce a globally aligned ECM network in 2-D culture as observed in scar tissue. ECM anisotropy develops after rapid initiation of a fibroblast supracellular
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Global, but not chondrocyte-specific, MT1-MMP deficiency in adult mice causes inflammatory arthritis Matrix Biol. (IF 6.9) Pub Date : 2023-08-19 Xiao-dan Xia, Govind Gill, Haiming Lin, Daniela M. Roth, Hong-mei Gu, Xiang-jiang Wang, Feng-yi Su, Adekunle Alabi, Maria Alexiou, Ziyang Zhang, Gui-qing Wang, Daniel Graf, Da-wei Zhang
Membrane-type I metalloproteinase (MT1-MMP/MMP14) plays a key role in various pathophysiological processes, indicating an unaddressed need for a targeted therapeutic approach. However, mice genetically deficient in Mmp14 show severe defects in development and growth. To investigate the possibility of MT1-MMP inhibition as a safe treatment in adults, we generated global Mmp14 tamoxifen-induced conditional
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Emilin2 fosters vascular stability by promoting pericyte recruitment Matrix Biol. (IF 6.9) Pub Date : 2023-08-12 Albina Fejza, Lucrezia Camicia, Greta Carobolante, Evelina Poletto, Alice Paulitti, Giorgia Schinello, Emanuele Di Siena, Renato Cannizzaro, Renato V. Iozzo, Gustavo Baldassarre, Eva Andreuzzi, Paola Spessotto, Maurizio Mongiat
Angiogenesis, the formation of the new blood vessels from pre-existing vasculature, is an essential process occurring under both normal and pathological conditions, such as inflammation and cancer. This complex process is regulated by several cytokines, growth factors and extracellular matrix components modulating endothelial cell and pericyte function. In this study, we discovered that the extracellular
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The extracellular matrix – immune microenvironment crosstalk in cancer therapy: Challenges and opportunities Matrix Biol. (IF 6.9) Pub Date : 2023-07-29 Lara Closset, Okan Gultekin, Sahar Salehi, Dhifaf Sarhan, Kaisa Lehti, Jordi Gonzalez-Molina
Targeting the tumour immune microenvironment (TIME) by cancer immunotherapy has led to improved patient outcomes. However, response to these treatments is heterogeneous and cancer-type dependant. The therapeutic activity of classical cancer therapies such as chemotherapy, radiotherapy, and surgical oncology is modulated by alterations of the TIME. A major regulator of immune cell function and resistance
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SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation Matrix Biol. (IF 6.9) Pub Date : 2023-08-02 Xinru Xue, Xi Zeng, Xiaoqian Wu, Kexin Mu, Yue Dai, Zhifeng Wei
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The clock transcription factor BMAL1 is a key regulator of extracellular matrix homeostasis and cell fate in the intervertebral disc Matrix Biol. (IF 6.9) Pub Date : 2023-07-24 Michal Dudek, Honor Morris, Natalie Rogers, Dharshika RJ Pathiranage, Sujitha Saba Raj, Danny Chan, Karl E Kadler, Judith Hoyland, Qing-Jun Meng
The circadian clock in mammals temporally coordinates physiological and behavioural processes to anticipate daily rhythmic changes in their environment. Chronic disruption to circadian rhythms (e.g., through ageing or shift work) is thought to contribute to a multitude of diseases, including degeneration of the musculoskeletal system. The intervertebral disc (IVD) in the spine contains circadian clocks
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Peptide location fingerprinting identifies structural alterations within basement membrane components in ageing kidney Matrix Biol. (IF 6.9) Pub Date : 2023-07-10 Alexander Eckersley, Mychel RPT Morais, Matiss Ozols, Rachel Lennon
During ageing, the glomerular and tubular basement membranes (BM) of the kidney undergo a progressive decline in function that is underpinned by histological changes, including glomerulosclerosis and tubular interstitial fibrosis and atrophy. This BM-specific ageing is thought to result from damage accumulation to long-lived extracellular matrix (ECM) protein structures. Determining which BM proteins
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SEMA7a primes integrin α5β1 engagement instructing fibroblast mechanotransduction, phenotype and transcriptional programming Matrix Biol. (IF 6.9) Pub Date : 2023-07-07 Hu P, Miller AE, Yeh CR, Bingham GC, Civelek M, Barker TH
Integrins are cellular receptors that bind the extracellular matrix (ECM) and facilitate the transduction of biochemical and biophysical microenvironment cues into cellular responses. Upon engaging the ECM, integrin heterodimers must rapidly strengthen their binding with the ECM, resulting in the assembly of force-resistant and force-sensitive integrin associated complexes (IACs). The IACs constitute
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Fibrolamellar carcinomas–growth arrested by paracrine signals complexed with synthesized 3-O sulfated heparan sulfate oligosaccharides Matrix Biol. (IF 6.9) Pub Date : 2023-07-02 Wencheng Zhang, Yongmei Xu, Xicheng Wang, Tsunekazu Oikawa, Guowei Su, Eliane Wauthier, Guoxiu Wu, Praveen Sethupathy, Zhiying He, Jian Liu, Lola M. Reid
Fibrolamellar carcinomas (FLCs), lethal tumors occurring in children to young adults, have genetic signatures implicating derivation from biliary tree stem cell (BTSC) subpopulations, co-hepato/pancreatic stem cells, involved in hepatic and pancreatic regeneration. FLCs and BTSCs express pluripotency genes, endodermal transcription factors, and stem cell surface, cytoplasmic and proliferation biomarkers
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TSG6 hyaluronan matrix remodeling dampens the inflammatory response during colitis Matrix Biol. (IF 6.9) Pub Date : 2023-06-29 Nansy Albtoush, Kimberly A. Queisser, Ash Zawerton, Mark E. Lauer, Ellen J. Beswick, Aaron C Petrey
In response to tissue injury, changes in the extracellular matrix (ECM) can directly affect the inflammatory response and contribute to disease progression or resolution. During inflammation, the glycosaminoglycan hyaluronan (HA) becomes modified by tumor necrosis factor stimulated gene-6 (TSG6). TSG6 covalently transfers heavy chain (HC) proteins from inter-α-trypsin inhibitor (IαI) to HA in a transesterification
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Absence of TRIC-B from type XIV Osteogenesis Imperfecta osteoblasts alters cell adhesion and mitochondrial function – A multi-omics study Matrix Biol. (IF 6.9) Pub Date : 2023-06-20 Milena Jovanovic, Apratim Mitra, Roberta Besio, Barbara Maria Contento, Ka Wai Wong, Alberta Derkyi, Michael To, Antonella Forlino, Ryan K Dale, Joan C Marini
Osteogenesis Imperfecta (OI) is a heritable collagen-related bone dysplasia characterized by bone fractures, growth deficiency and skeletal deformity. Type XIV OI is a recessive OI form caused by null mutations in TMEM38B, which encodes the ER membrane intracellular cation channel TRIC-B. Previously, we showed that absence of TMEM38B alters calcium flux in the ER of OI patient osteoblasts and fibroblasts
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ADAMTS3 restricts cancer invasion in models of early breast cancer progression through enhanced fibronectin degradation Matrix Biol. (IF 6.9) Pub Date : 2023-06-17 Shayin V. Gibson, Elizabeta Madzharova, Amandine C. Tan, Michael D. Allen, Ulrich auf dem Keller, J. Louise Jones, Edward P. Carter, Richard P. Grose
Proteases have long been associated with cancer progression, due to their ability to facilitate invasion upon matrix remodelling. However, proteases are not simply degraders of the matrix, but also play fundamental roles in modulating cellular behaviour through the proteolytic processing of specific substrates. Indeed, proteases can elicit both pro- and anti- tumorigenic effects depending on context
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Cell differentiation and matrix organization are differentially affected during bone formation in osteogenesis imperfecta zebrafish models with different genetic defects impacting collagen type I structure Matrix Biol. (IF 6.9) Pub Date : 2023-06-17 Valentina Daponte, Francesca Tonelli, Cecilia Masiero, Delfien Syx, Chloé Exbrayat-Héritier, Marco Biggiogera, Andy Willaert, Antonio Rossi, Paul J. Coucke, Florence Ruggiero, Antonella Forlino
Osteogenesis imperfecta (OI) is a family of rare heritable skeletal disorders associated with dominant mutations in the collagen type I encoding genes and recessive defects in proteins involved in collagen type I synthesis and processing and in osteoblast differentiation and activity. Historically, it was believed that the OI bone phenotype was only caused by abnormal collagen type I fibrils in the
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Collagen VI deposition mediates stromal T cell trapping through inhibition of T cell motility in the prostate tumor microenvironment Matrix Biol. (IF 6.9) Pub Date : 2023-06-16 Hawley C. Pruitt, Ya Guan, Hudson Liu, Alexis E Carey, W. Nathaniel Brennen, Jiayun Lu, Corrine Joshu, Ashani Weeraratna, Tamara L. Lotan, T.S. Karin Eisinger-Mathason, Sharon Gerecht
The tumor extracellular matrix (ECM) is a barrier to anti-tumor immunity in solid tumors by disrupting T cell-tumor cell interaction underlying the need for elucidating mechanisms by which specific ECM proteins impact T cell motility and activity within the desmoplastic stroma of solid tumors. Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate
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Endothelial basement membrane laminins - new players in mouse and human myoendothelial junctions and shear stress communication Matrix Biol. (IF 6.9) Pub Date : 2023-06-11 Anna-Liisa Luik, Melanie-Jane Hannocks, Sophie Loismann, Kishan Kapupara, Manuela Cerina, Miesje van der Stoel, Yaroslav Tsytsyura, Nataliya Glyvuk, Caroline Nordenvall, Jürgen Klingauf, Stephan Huveneers, Sven Meuth, Lars Jakobsson, Lydia Sorokin
Basement membranes (BMs) are critical but frequently ignored components of the vascular system. Using high-resolution confocal imaging of whole-mount-stained mesenteric arteries, we identify integrins, vinculin, focal adhesion kinase (FAK) and several BM proteins including laminins as novel components of myoendothelial junctions (MEJs), anatomical microdomains that are emerging as regulators of cross-talk
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Matrix stiffening facilitates the collective invasion of breast cancer through the periostin-integrin mechanotransduction pathway Matrix Biol. (IF 6.9) Pub Date : 2023-05-23 Tiantian Wu, Shanshan Xiong, Mimi Chen, Bjorn T. Tam, Wei Chen, Ke Dong, Zhenling Ma, Zhe Wang, Gaoliang Ouyang
Matrix rigidity is a critical contributor to tumor progression; however, whether and how matrix stiffness modulates the collective invasion of tumor cells remain unknown. Here we demonstrate that increased matrix stiffness activates YAP to promote the secretion of periostin (POSTN) in cancer-associated fibroblasts, which in turn augments the matrix rigidity of mammary glands and breast tumor tissues
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TGFβ-2 haploinsufficiency causes early death in mice with Marfan syndrome Matrix Biol. (IF 6.9) Pub Date : 2023-05-20 Nalani Sachan, Colin K.L. Phoon, Lior Zilberberg, Matthias C. Kugler, Taylor Ene, Shana B. Mintz, Sae-Il Murtada, Dar Weiss, Glenn I. Fishman, Jay D. Humphrey, Daniel B. Rifkin
To assess the contribution of individual TGF-β isoforms to aortopathy in Marfan syndrome (MFS), we quantified the survival and phenotypes of mice with a combined fibrillin1 (the gene defective in MFS) hypomorphic mutation and a TGF-β1, 2, or 3 heterozygous null mutation. The loss of TGF-β2, and only TGF-β2, resulted in 80% of the double mutant animals dying earlier, by postnatal day 20, than MFS only
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3-O sulfation of syndecan-1 mediated by the sulfotransferase HS3ST3a1 enhances myeloma aggressiveness Matrix Biol. (IF 6.9) Pub Date : 2023-05-16 L. Baert, B. Manfroi, M. Quintero, O. Chavarria, P.V. Barbon, E. Clement, A. Zeller, T. Van Kuppevelt, N. Sturm, J. Moreaux, A. Tveita, B. Bogen, T. McKee, B. Huard
Multiple myeloma is a hematological neoplasm derived from plasma cells invariably developing in the bone marrow (BM). The persisting clinical challenge in MM resides in its high ability to resist drugs as shown by the frequent relapses observed in patients regardless of the treatment applied. In a mouse model of MM, we identified a subpopulation of cells harboring increased resistance to current MM
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Secreted ADAMTS-like 2 promotes myoblast differentiation by potentiating WNT signaling Matrix Biol. (IF 6.9) Pub Date : 2023-05-14 Nandaraj Taye, Mukti Singh, Clair Baldock, Dirk Hubmacher
Myogenesis is the process that generates multinucleated contractile myofibers from muscle stem cells during skeletal muscle development and regeneration. Myogenesis is governed by myogenic regulatory transcription factors, including MYOD1. Here, we identified the secreted matricellular protein ADAMTS-like 2 (ADAMTSL2) as part of a Wnt-dependent positive feedback loop, which augmented or sustained MYOD1
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CaMKII inhibition due to TRIC-B loss-of-function dysregulates SMAD signaling in osteogenesis imperfecta Matrix Biol. (IF 6.9) Pub Date : 2023-05-11 Roberta Besio, Barbara M. Contento, Nadia Garibaldi, Marta Filibian, Stephan Sonntag, Doron Shmerling, Francesca Tonelli, Marco Biggiogera, Marisa Brini, Andrea Salmaso, Milena Jovanovic, Joan C. Marini, Antonio Rossi, Antonella Forlino
Ca2+ is a second messenger that regulates a variety of cellular responses in bone, including osteoblast differentiation. Mutations in trimeric intracellular cation channel B (TRIC-B), an endoplasmic reticulum channel specific for K+, a counter ion for Ca2+flux, affect bone and cause a recessive form of osteogenesis imperfecta (OI) with a still puzzling mechanism. Using a conditional Tmem38b knock out
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Positive feedback loops between fibroblasts and the mechanical environment contribute to dermal fibrosis Matrix Biol. (IF 6.9) Pub Date : 2023-05-08 Liang Zhu, Lechen Liu, Aoli Wang, Jinwen Liu, Xin Huang, Tao Zan
Dermal fibrosis is characterized by excessive deposition of extracellular matrix in the dermis and affects millions of people worldwide and causes limited movement, disfigurement and psychological distress in patients. Fibroblast dysfunction of plays a central role in the pathogenesis of dermal fibrosis and is controlled by distinct factors. Recent studies support the hypothesis that fibroblasts can
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Matricellular proteins in atherosclerosis development Matrix Biol. (IF 6.9) Pub Date : 2023-04-20 Naveed Pervaiz, Ishita Kathuria, Ravi Varma Aithabathula, Bhupesh Singla
The extracellular matrix (ECM) is an intricate network composed of various multi-domain macromolecules like collagen, proteoglycans, and fibronectin, etc., that form a structurally stable composite, contributing to the mechanical properties of tissue. However, matricellular proteins are non-structural, secretory extracellular matrix proteins, which modulate various cellular functions via interacting
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Tumor-Associated Fibrosis Impairs the Response to Immunotherapy Matrix Biol. (IF 6.9) Pub Date : 2023-04-18 Angha Naik, Andrew Leask
Previously, impaired responses to immunotherapy in cancer had been attributed mainly to inherent tumor characteristics (tumor cell intrinsic factors) such as low immunogenicity, (low) mutational burden, weak host immune system, etc. However, mapping the responses of immunotherapeutic regimes in clinical trials for different types of cancer has pointed towards an obvious commonality – that tumors with