Allergic contact dermatitis (ACD) is a delayed-type IV hypersensitivity response driven by innate and adaptive immune cells. While specific immune regulations of these cell types are amply elucidated, their regulations by extracellular matrix (ECM) components and T cell mediated adaptive immunity in ACD remains unclear. Lumican and biglycan are ECM proteoglycans abundant in the dermis and lymph node

Basement membranes (BMs) are planar extracellular matrices that line the basal surfaces of epithelia and are essential components of most organs. During development, BMs can also play instructive roles in shaping the tissues to which they belong, but how they do so is incompletely understood. The Drosophila egg chamber has become a premier system to study this aspect of BM biology due to the ostensible

In breast cancer, mechanotransduction from stiffened extracellular matrix (ECM) drives proliferation and invasion. Here, we use a model of matrix stiffening mimicking progression of breast ductal carcinoma in situ to invasive ductal carcinoma. Quantitative mass spectrometry identified enrichment of ECM-stiffness upregulated mevalonate pathway enzymes, indicating sterol/isoprenoid metabolism reprogramming

Intestinal fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) in the bowel wall. Complications, such as strictures that require surgical intervention in a large proportion of patients, are considered an inevitable consequence of chronic inflammation in inflammatory bowel disease (IBD) and leads to severe complications. The study of intestinal fibrosis in IBD has been

In response to mechanical stimuli, chondrocytes adapt their transcriptional activity, thereby shaping the cellular mechano-response; however, it remains unclear whether the activation of cell surface receptors during mechanical loading converge in the activation of the same mechano-response genes, or whether pathway-specific genes can be defined. We aimed to determine whether load-activated FGF/FGFR

Stromal components of the tumour microenvironment, such as cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM), are actively involved in tumorigenesis. CAFs and the ECM co-evolve with resultant molecular and mechanical pressure on tumour cells mediated by CAFs via the ECM. Meanwhile, ECM fibers determine CAF differentiation and activity, establishing a protumorigenic feed-forward

LRP1 is a multifunctional endocytosis receptor involved in the regulation of cancer cell aggressiveness, fibroblast phenotype and angiogenesis. In breast cancer microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role in matrix remodeling and tumor niche composition. LRP1 expression was described in fibroblasts and CAFs but remains poorly understood regarding its impact on endothelial

Type IV collagen is a large triple helical molecule that forms a covalently cross-linked network within basement membranes (BMs). Type IV collagen networks play key roles in mechanically supporting tissues, shaping organs, filtering blood, and cell signaling. To ensure tissue health and function, all aspects of the type IV collagen life cycle must be carried out accurately. However, the large triple

The cerebrovascular basement membrane (BM) is a key component of the blood-brain barrier (BBB). The BM provides structural support for brain microvascular endothelial cells and the supporting cells of the neurovascular unit, and facilitates cell signaling through adhesion receptors, regulates the concentration of soluble factors, and serves as an additional barrier for transport. However, our understanding

Collagen is the most abundant protein in mammals, significantly contributing to cancer progression. Cells express two primary well-conserved collagen receptors, integrins and discoidin domain receptors (DDRs), which bind collagen on distinct sites, suggesting that cancer cells must integrate both signals to decide their fate. The crosstalk between integrins and DDRs mediated by collagen binding produces

Pentraxin-3 (PTX3) is a secreted protein with roles in the stabilisation of hyaluronan-rich extracellular matrices involved in reproductive biology and inflammatory processes, as well as additional functions in innate immunity and cancer. Our recent structural studies (Shah et al., 2025; DOI:10.1016/j.matbio.2025.01.002), involving X-ray crystallography, cryo-electron microscopy (cryoEM) and AlphaFold

Elastin is a connective tissue protein, produced from the ELN gene, that provides elasticity and recoil to tissues that stretch, such as the large arteries of the body, lung parenchyma, skin, ligaments and elastic cartilages. It is produced as a soluble monomer, tropoelastin, that when cross-linked in the extracellular space generates a polymer that is extraordinarily stable, with a predicted half-life

Perlecan is an essential multi-domain, disulfide bond rich basement membrane protein. Mutations in perlecan cause Schwartz-Jampel syndrome and dyssegmental dysplasia. While there has been a large body of experimental work reported on perlecan, there is only minimal structural information available to date. There is no prior structural data for region 3 of perlecan in which some Schwartz-Jampel syndrome

Collagen type I (COL1) is the most abundant protein in the human body and is a main component in the extracellular matrix. The COL1 structure vastly influences normal tissue homeostasis, and changes in the matrix drive progression in multiple diseases. Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity in many Western countries; alterations in the extracellular matrix turnover

The blood-brain barrier (BBB) is a dynamic structure that maintains brain homeostasis. BBB breakdown is a key pathological hallmark of almost all neurological diseases. Although the regulation of BBB integrity by different cells has been extensively studied, the function of its non-cellular component—the basal lamina in BBB regulation remains largely unknown. Laminin, a trimeric protein with multiple

Vocal fold scarring, the most common cause of poor voice after airway injury, involves the transition of vocal fold fibroblasts to contractile myofibroblasts. Vocal fold myofibroblasts can be characterized by significant extracellular matrix (ECM) secretion and stress fiber formation. Biochemical signals, such as transforming growth factor (TGF)-β1, and biophysical cues, such as matrix stiffening,

The collagen triple helix is one of the structurally simplest protein motifs that still holds a lot of secrets. The Gly-X-Y repeat is a business card of collagens, where Gly is required for the tight packing of three helices into a superhelix and X and Y residues are important for stabilizing the triple helix and communicating with the world. On its way to a functional molecule, collagen sequences

Syndecan-4 (SDC4), a heparan sulfate proteoglycan, is aberrantly expressed in breast cancer and plays a significant role in tumor progression by influencing cell proliferation and promoting invasive growth. This study aimed to characterize its role in the tumor microenvironment by analyzing the contribution of SDC4 to vasculogenic mimicry (VM) and angiogenesis in human breast cancer cells. We silenced

The skin, as a barrier organ meeting constant mechanical challenges, is equipped with multiple adhesive structures that collectively support resilient, yet flexible attachment of its epithelium –the epidermis to its mesenchyme – the dermis. One such structure is the collagen VII-composed anchoring fibril, which provides firm anchorage of the epidermal basement membrane to the underlying interstitial

Collagen stroma interactions within the extracellular microenvironment of breast tissue play a significant role in breast cancer, including risk, progression, and outcomes. Hydroxylation of proline (HYP) is a common post-translational modification directly linked to breast cancer survival and progression. Changes in HYP status lead to alterations in epithelial cell signaling, extracellular matrix remodeling

Rapid progress has been made in the exciting field of secretome research in health and disease. The tumor secretome, which is a significant proportion of the tumor proteome, is secreted into the extracellular space to promote intercellular communication and thus tumor progression. Among the many molecules of the secretome, integrins and matrix metalloproteinase 14 (MMP14) stand out as the interplay

The role of cells of the hematopoietic lineage in fibrosis is controversial. Here we evaluate the contribution of Col I+/CD45+ cells (fibrocytes) to lung fibrosis. Systemic bleomycin treatment was used to induce fibrosis in a bone marrow transplant and two transgenic mouse models. Lung cells from these mice were analyzed by flow cytometry, both immediately upon release from the tissue or following

Arterial endothelial cells (ECs) reside in a complex biomechanical environment. ECs sense and respond to wall shear stress. Low and oscillatory wall shear stress is characteristic of disturbed flow and commonly found at arterial bifurcations and around atherosclerotic plaques. Disturbed flow is pro-inflammatory to ECs. Arteries also stiffen with aging and/or the onset of vascular disease. ECs sense

Pentraxin-3 (PTX3) is an octameric protein, comprised of eight identical protomers, that has diverse functions in reproductive biology, innate immunity and cancer. PTX3 interacts with the large polysaccharide hyaluronan (HA) to which heavy chains (HCs) of the inter-α-inhibitor (IαI) family of proteoglycans are covalently attached, playing a key role in the (non-covalent) crosslinking of HC•HA complexes

The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also around synapses and in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of

Release of growth factors in the tissue microenvironment is a critical process in the repair and regeneration of periodontal tissues, regulating fibroblast behavior and phenotype. As a result of the complex architecture of the periodontium, distinct fibroblast populations in the periodontal ligament and gingival connective tissue exist in close proximity. Growth factor therapies for periodontal regeneration

Advanced Glycation End Products (AGEs) are the end result of the irreversible, non-enzymatic glycation of proteins by reducing sugars. These chemical modifications accumulate with age and have been associated with various age-related and diabetic complications. AGEs predominantly accumulate on proteins with slow turnover rates, of which collagen is a prime example. Glycation has been associated with

Disrupting the interaction between matrix metalloproteinase-7 (MMP-7) and syndecan-2 (SDC-2) can yield anticancer effects in colon cancer cells. Here, a single-chain variable fragment (scFv) targeting the pro-domain of MMP-7 was generated as a potential candidate anticancer agent. Among the generated scFvs, those designated 1B7 and 1C3 showed the strongest abilities to inhibit the ability of MMP-7

Obesity is a growing concern in the US and world-wide, associated with an increased risk for several cardiometabolic diseases, including metabolic associated steatotic liver disease (MASLD). Currently, therapeutic interventions to prevent and/or treat MASLD are limited, and research is needed to identify new therapeutic targets. The specific-sized 35 kDa fragment of hyaluronan (HA35), has gut protective

The lung is a highly vascularized tissue that often harbors metastases from various extrathoracic malignancies. Lung parenchyma consists of a complex network of alveolar epithelial cells and microvessels, structured within an architecture defined by basement membranes. Consequently, understanding the role of the extracellular matrix (ECM) in the growth of lung metastases is essential to uncover the

Extracellular vesicles (EVs) mediate intercellular communication. EVs are composed of a lipid bilayer and contain cytosolic proteins and RNAs. Studies highlight EVs striking functions in cell-cell crosstalk. Here, we found that small EVs can transfer functional signaling molecules through their lipid bilayer and participate in skin homeostasis. We identified a transmembrane protein CD98hc (a.k.a. SLC3A2)

Osteoarthritis (OA) is a highly prevalent joint disease, affecting millions of people worldwide and characterized by degradation of articular cartilage, subchondral bone remodeling and low-grade inflammation, leading to pain, stiffness and disability. Cartilage Oligomeric Matrix Protein (COMP) is a major structural component of cartilage and its degradation has been proposed as a marker of OA severity/progression

Pancreatic stellate cells (PSCs) produce a collagen-rich connective tissue in chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC). Ca2+-permeable ion channels such as ORAI1 are known to affect PSC proliferation and myofibroblastic phenotype. However, it is unknown whether these channels play a role in collagen secretion.

Vascular Ehlers-Danlos syndrome (vEDS) arises from mutations in collagen-III, a major structural component of the extracellular matrix (ECM) in vascularized tissues, including blood vessels. Fibrillar collagens form a triple-helix that is characterized by a canonical (Gly-X-Y)n sequence. The substitution of another amino acid for Gly within this conserved repeating sequence is associated with several

Integrins, a group of transmembrane receptors, play a crucial role in mediating the interactions between cells and extracellular matrix (ECM) proteins. The intracellular signaling initiated by these cell-matrix interactions in leukocytes mediates many essential cellular processes such as survival, migration, metabolism, and other immunological functions. Macrophages, as phagocytes, participate in both

Tendon and ligament injuries are highly prevalent but heal poorly, even with proper care. Restoration of native tissue function is complicated by the fact that these tissues vary anatomically in terms of their mechanical properties, composition, and structure. These differences develop as adaptations to diverse mechanical demands; however, pathology may alter the loads placed on the tissue. Musculoskeletal

Fibrillin-1, an extracellular matrix (ECM) protein encoded by the FBN1 gene, serves as a microfibril scaffold crucial for elastic fiber formation and homeostasis in pliable tissue such as the skin. Aside from causing Marfan syndrome, some mutations in FBN1 result in scleroderma, marked by hardened and thicker skin which limits joint mobility. Here, we describe a tight skin phenotype in the Fbn1G234D/G234D

Integrin α6β4 subunits and type XVII collagen are critical transmembrane proteins involved in cell-matrix adhesion in skin, while laminin 332 serves as their ligand in the basement membrane zone (BMZ). Those proteins contribute to the composition of hemidesmosomes (HDs) and pathogenic variants in their corresponding genes cause junctional epidermolysis bullosa (JEB). Although the genotype-phenotype

Mechanical properties of the extracellular matrix (ECM) critically regulate a number of important cell functions including growth, differentiation and migration. Type I collagen and glycosaminoglycans (GAGs) are two primary components of ECMs that contribute to mammalian tissue mechanics, with the collagen fiber network sustaining tension, and GAGs withstanding compression. The architecture and stiffness

The extracellular matrix (ECM) serves as a physical scaffold for tissues that is composed of structural proteins such as laminins, collagens, proteoglycans and fibronectin, forming a three dimensional network, and a wide variety of other matrix proteins with ECM-remodeling and signaling functions. The activity of ECM-associated signaling proteins is tightly regulated. Thus, the ECM serves as a reservoir

The brain's extracellular matrix (ECM) is crucial for neural circuit functionality, synaptic plasticity, and learning. While the role of the ECM in excitatory synapses has been extensively studied, its influence on inhibitory synapses, particularly on GABAergic long-term plasticity, remains poorly understood. This study aims to elucidate the effects of ECM components on inhibitory synaptic transmission

Integrins are cellular transmembrane receptors that physically connect the cytoskeleton with the extracellular matrix. As such, they are positioned to mediate cellular responses to microenvironmental cues. Importantly, integrins also regulate their own microenvironment through secreted factors, also known as the integrin-mediated secretome. Epidermal integrins, or integrins expressed by keratinocytes

Spinal movement in both upright and recumbent positions generates changes in physicochemical stresses including hydrostatic pressure (HP), deviatoric stress, and confinement within the intradiscal compartment. The nucleus pulposus (NP) of the intervertebral disc is composed of highly negatively charged extracellular matrix (ECM), which increases osmotic pressure (OP) and generates tissue swelling.

Solid epithelial cancers with significant desmoplasia are characterized by an excessive deposition of collagen-based matrix, which often supports tumor progression. However, the mechanism of how collagen receptors mediate collagen fibrillogenesis still remains mostly unclear.

Corneal endothelial cells (CECs) are essential for maintaining corneal transparency and hydration through their barrier and pump functions. The COL8A2 gene encodes a component of the extracellular matrix of the cornea, which is crucial for the normal functioning of these cells. Mutations in COL8A2 are linked to corneal dystrophies, emphasizing the gene's importance in corneal health. The purpose of

Cancer-associated myofibroblasts (mCAFs) represent a significant component of the tumor microenvironment due to their contributions to extracellular matrix (ECM) remodeling. The pro-tumor mechanisms of extracellular vesicles (EVs) by regulating mCAFs and related collagens remain poorly understood in oral squamous cell carcinoma (OSCC). In this study, through analysis of single-cell sequencing data

Cranial sutures function as growth centers for calvarial bones. Abnormal suture closure will cause permanent cranium deformities. MMP9 is a member of the gelatinases that degrades components of the extracellular matrix. MMP9 has been reported to regulate bone development and remodeling. However, the function of MMP9 in cranial suture development is still unknown. Here, we identified that the expression

The heparan sulfate (HS) 6-O-endosulfatases or the Sulfs (Sulf1 and Sulf2) are the only known enzymes that can modify HS sulfation status extracellularly and have been shown to regulate diverse biological processes. The role of the Sulfs in bone marrow (BM) hematopoiesis is not known. In this study, we generated a novel mouse line with myeloid-specific deletion of the Sulfs by crossing Sulf1/2 double

Atherosclerotic calcification often coincides with osteoporosis, suggesting a potential interplay between bone and vascular mineralization. Osteoblast-derived matrix vesicles (Ost-MVs), pivotal in bone mineralization, have emerged as potential contributors to ectopic vascular calcification. However, the precise role of Ost-MVs in vascular calcification and the underlying mechanisms remain elusive.

Osteosarcoma (OS) mortality stems from lung metastases. Matrix metalloproteinases (MMPs) facilitate metastatic dissemination by degrading extracellular matrix components. Herein we studied the impact of targeted MMP downregulation on OS metastasis. Differential gene expression analysis of human OS cell lines revealed high MMP9 expression in the majority of OS cell lines. Furthermore, 143B, a metastatic

PCPE-2 was discovered at the beginning of this century, and was soon identified as a close homolog of PCPE-1 (procollagen C-proteinase enhancer 1). After the demonstration that it could also stimulate the proteolytic maturation of fibrillar procollagens by BMP-1/tolloid-like proteinases (BTPs), PCPE-2 did not attract much attention as it was thought to fulfill the same functions as PCPE-1 which was

Fibronectin (FN) serves as a critical organizer of extracellular matrix networks in two principal isoforms, the plasma FN and the cellular FN. While FN's pivotal role in various organ systems, including the blood vasculature, is well-established, its contribution to the development of the skeletal system is much less explored. Furthermore, the pathomechanisms of spondyloepiphyseal dysplasia caused

The skin seems to rejuvenate upon exposure to factors within the circulation of young organisms. Intrinsic factors that modulate skin aging are poorly understood. We used heterochronic parabiosis and aptamer-based proteomics to identify serum-derived rejuvenating factors. We discovered a novel extracellular function of hyaluronan and proteoglycan link protein 1 (HAPLN1). Its serum levels decreased

Fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) and constitutes a central pathophysiological process that underlies tissue dysfunction, across organs, in multiple chronic diseases and during aging. Myocardial fibrosis is a key contributor to dysfunction and failure in numerous diseases of the heart and is a strong predictor of poor clinical outcome and mortality. The

Metabolic syndrome and diabetes in obese individuals are strong risk factors for development of inflammatory bowel disease (IBD) and colorectal cancer. The pathogenic mechanisms of low-grade metabolic inflammation, including chronic hyperglycemic stress, in disrupting gut homeostasis are poorly understood. In this study, we sought to understand the impact of a hyperglycemic environment on intestinal

Fibronectin (FN) is a ubiquitous extracellular matrix glycoprotein essential for the development of various tissues. Mutations in FN cause a unique form of spondylometaphyseal dysplasia, emphasizing its importance in cartilage and bone development. However, the relevance and functional role of FN during skeletal development has remained elusive. To address these aspects, we have generated conditional

Collagens have dual functions in the extracellular matrix (ECM), acting as both structural components and signaling molecules in matricellular communication. Although collagen molecules share a common triple helix motif, the supramolecular organization helps classify them into nearly 30 different types of collagens. Collagen type VIII is a non-fibrillar, short-chain, network-forming collagen that is

Skeletal muscle fibrosis is defined as the excessive accumulation of extracellular matrix (ECM) components and is a hallmark of muscular dystrophies. Fibro-adipogenic progenitors (FAPs) are the main source of ECM, and thus have been strongly implicated in fibrogenesis. In skeletal muscle fibrotic models, including muscular dystrophies, FAPs undergo dysregulations in terms of proliferation, differentiation