The role of transforming growth factor β TGFβ/activin signaling in wound repair and regeneration is highly conserved in the animal kingdom. Various studies have shown that TGF-β/activin signaling can either promote or inhibit different aspects of the regeneration process (i.e., proliferation, differentiation, and re-epithelialization). It has been demonstrated in several biological systems that some

CCN2, formerly termed Connective Tissue Growth Factor, is a protein belonging to the Cellular Communication Network (CCN)-family of secreted extracellular matrix-associated proteins. As a matricellular protein it is mainly considered to be active as a modifier of signaling activity of several different signaling pathways and as an orchestrator of their cross-talk. Furthermore, CCN2 and its fragments

Targeted gene disruption in mice has provided valuable insights into the functions of matricellular proteins. Apart from missense and loss of function mutations that have been associated with inherited diseases, however, their functions in humans remain unclear. The availability of deep exome sequencing data from over 140,000 individuals in the Genome Aggregation Database provided an opportunity to

Fibroblast growth factor 1 (FGF-1) is the first FGF family member, and it induces proliferation of fibroblasts and other types of the cells. However, recent studies are uncovering unexpected functions of this molecule. Our previous study redefined this growth factor as a catabolic molecule produced in cartilage upon metabolic insult. Indeed, FGF-1 was found to repress the gene expression of cellular

Fibrosis is perpetuated by an autocrine, pro-adhesive signaling loop maintained by the synthetic and contractile abilities of myofibroblasts and the stiff, highly-crosslinked extracellular matrix. Transcriptional complexes that are exquisitely responsive to mechanotransduction include the co-activator YAP1, which regulates the expression of members of the CCN family of matricellular proteins such as

The role of autophagy and lysosomal degradation pathway in the regulation of skeletal muscle metabolism was previously studied. However, underlying molecular mechanisms are poorly understood. L-lactate which is utilized as an energetic substrate by skeletal muscle can also augment genes expression related to metabolism and up-regulate those being responsive to reactive oxygen species (ROS). Since ROS

Calcium (Ca2+) signaling has a major role in regulating a wide range of cellular mechanisms, including gene expression, proliferation, metabolism, cell death, muscle contraction, among others. Recent evidence suggests that ~ 1600 genes are related to the Ca2+ signaling. Some of these genes’ expression is altered in several pathological conditions, including different cancer types, and epigenetic mechanisms

The author was omitted from the original article and is Annick Perbal, International CCN Society.

Growth hormone releasing hormone (GHRH) antagonists enhance endothelial barrier function and counteract the LPS-induced lung endothelial hyperpermeability, the cardinal feature of the acute respiratory distress syndrome (ARDS). The unfolded protein response (UPR) is a multifaceted molecular mechanism, strongly involved in tissue defense against injury. The current study introduces the induction of

Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a serine/threonine-protein kinase belonging to the Ca2+/calmodulin-dependent protein kinase subfamily. CAMKK2 has an autocatalytic site, which gets exposed when Ca2+/calmodulin (CAM) binds to it. This results in autophosphorylation and complete activation of CAMKK2. The three major known downstream targets of CAMKK2 are 5′-adenosine monophosphate

The galanin receptor family of proteins is present throughout the central nervous system and endocrine system. It comprises of three subtypes—GalR1, GalR2, and GalR3; all of which are G-protein-coupled receptors. Galanin predominantly acts as an inhibitory, hyper-polarizing neuromodulator, which has several physiological as well as pathological functions. Galanin has a role in mediating food intake

Due to the steadily rising morbidity and mortality, thyroid cancer remains the most commonly seen endocrine cancer. The present study attempted to investigate the mechanism from the perspective of long non-coding RNA (lncRNA) regulation. We identified 53 markedly increased lncRNAs in thyroid cancer samples according to TCGA data. Among them, high lncRNA DIO3OS expression was a risk factor for thyroid

This study aimed to elucidate the underlying molecular mechanism of photobiomodulation (PBM) in attenuating oxidative stress in diabetic wounded fibroblast cells. Cell models were exposed to PBM at a wavelength of 660 nm (fluence of 5 J/cm2, and power density of 11.2 mW/cm2) or 830 nm (fluence of 5 J/cm2, and power density of 10.3 mW/cm2). Non-irradiated cell models were used as controls. Cellular

Hepatoblastoma (HB) is one of the most common liver malignancies in children, while the molecular basis of the disease is largely unknown. Therefore, this study aims to explore the key genes and molecular mechanisms of the pathogenesis of HB using a bioinformatics approach. The gene expression dataset GSE131329 was used to find differentially expressed genes (DEGs). Functional and enrichment analyses

The original version of this article unfortunately requires correction where the name of a methyltransferase was represented wrongly.

The original version of this article unfortunately contained a mistake.

Prostaglandin signaling controls a wide range of biological processes from blood pressure homeostasis to inflammation and resolution thereof to the perception of pain to cell survival. Disruption of normal prostanoid signaling is implicated in numerous disease states. Prostaglandin signaling is facilitated by G-protein-coupled, prostanoid-specific receptors and the array of associated G-proteins. This

In the past two decades, two beta-coronaviruses, severe acute respiratory syndrome-related coronavirus (SARS-CoV-1) and the Middle East respiratory syndrome-related coronavirus (MERS-CoV), have infected approximately 8000 and 2500 across the globe, respectively (de Wit et al. 2016; Amanat and Krammer 2020). The current viral pandemic, caused by SARS-CoV-2, has already affected 4.23 M in less than a

Ovarian cancer is the most lethal gynecological malignancy and molecular mechanisms of its progression and metastasis are not completely understood. Some members of GAB (GRB2-associated binding) protein family have been reported to be involved in tumor cell proliferation and metastasis in various cancer types. In the present study, we analyzed the expression of GAB proteins (GAB1, GAB2 and GAB3) in

The capability of spermatozoa to directly influence maternal gene expression is already established. Indeed, some of the changes induced by spermatozoa may have a direct functional importance in the pre-conceptional period. Although the mechanisms underlying these sperm-maternal interactions are not well characterized, it is possible that they could involve ligands that are released from the spermatozoa

The current pandemic caused by the SARS-CoV-2 has claimed over a half a million lives within a very short span of time. A therapeutic drug which could prevent the entry and propagation of the virus is the need of the hour. Several lines of evidence collected from experimental studies older than three decades have pointed out the fact that inhibiting calcium entry into cells can affect vital steps in

Biomechanical stresses are closely associated with cardiovascular development and diseases. In vivo, vascular smooth muscle cells are constantly stimulated by biomechanical factors caused by increased blood pressure leading to the non-specific activation of cell transmembrane proteins. Thus, various intracellular signal molecules are simultaneously activated via signaling cascades, which are closely

The CCN family of matricellular proteins are recognized bona fide targets for therapeutically targeting so-called chronic inflammatory diseases, including fibrosis and cancers. The majority of the work supporting this contention has been derived from examining CCN2, formerly, and unhelpfully, termed “connective tissue growth factor.” Both CCN2, and its related protein, CCN1, formerly termed “cysteine-rich

During the last stages of wound healing, myofibroblasts differentiate mainly from fibroblasts. Myofibroblasts from normal skin wounds (Wmyo) can communicate with its surrounding using secreted factors. They also have the capacity to produce microvesicles (MVs), a type of extracellular vesicles, as mediators of intercellular communication. MVs cargo are potentially capable of regulating the behavior

Cancer cells are able to release high amounts of extracellular vesicles, thereby conditioning the normal cells in the surrounding tissue and/or in distant target organs. In the context of bone cancers, previous studies suggested that osteosarcoma cancer cells produce transforming extracellular vesicles able to induce a tumour-like phenotype in normal recipient cells. Indeed, phosphoinositide-specific

Appropriate tools for monitoring sarcoma progression are still limited. The aim of the present study was to investigate the value of miR-34a-5p (miR34a) as a circulating biomarker to follow disease progression and measure the therapeutic response. Stable forced re-expression of miR34a in Ewing sarcoma (EWS) cells significantly limited tumor growth in mice. Absolute quantification of miR34a in the plasma

Circular RNAs(CircRNAs), a new class of non-coding RNAs, possess significant capabilities of gene regulation and are disrupted in various diseases, including diabetes mellitus (DM). However, the underlying mechanism of CircRNAs in DM and diabetic complications remains illusive. A recent study published by Liu et al. (Proc Natl Acad Sci USA 116:7455-7464, 2019) shown that a novel diabetic retinopathy

Lung adenocarcinoma (LA) is a subtype of lung cancer that accounts for about 40% of all lung cancers. Analysis of molecular mechanisms controlling this cancer can help scientists to detect, control and treat LA. Here, a microarray dataset (GSE118370) containing six normal lung (NL) and six LA samples was screened using GEO2R to find differentially expressed genes (DEGs). Then, DAVID, KEGG and ChEA

One of the first targets proposed as an anti-fibrotic therapy was CCN2. Proof of its involvement in fibrosis was initially difficult, due to the lack of appropriate reagents and general understanding of the molecular mechanisms responsible for persistent fibrosis. As these issues have been progressively resolved over the last twenty-five years, it has become clear that CCN2 is a bone fide target for

COVID-19 is a respiratory disease. A recent report in Lancet examined, retrospectively, 137 patients with COVD-19. Patients that died had elevated IL-6 levels and acute respiratory distress syndrome. These data have obvious implications for how to control mortality in COVID-19.

Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti-CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs

This review focuses on current advances in researches of gasdermin family. The distinctive expression patterns and biological roles of members in this family were discussed. Most of them exhibit pore-forming activity on cell membranes and are executors for programmed cell death with cytokines release, and play roles in cancers and inflammation-driven diseases. Therefore, they can be used as potential

CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). In this study, we aimed to explore the anticancer effects of CUDC-907 on human breast cancer cells. Our results showed that CUDC-907 effectively inhibited breast cancer cell proliferation. Flow cytometry analysis revealed that CUDC-907 induced cell cycle arrest and apoptosis in breast cancer

IRE1α endonuclease is a key regulator of endoplasmic reticulum (ER) stress that controls cell survival/apoptosis in cancers. Inhibition of IRE1α endonuclease leads to decreased splice XBP1 which decreases cell proliferation and increases cell death in cancer cells. Therefore, this study investigated the effects and mechanism of STF-083010 (an IRE1α inhibitor) on the cell growth/apoptosis of ovarian

Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) pathway. Although our previous study has proved the efficacy of Erlotinib in head and neck squamous cell carcinoma (HNSCC), it has also demonstrated poor clinical response rates and disappointing results in clinical trials for HNSCC to date. In this study, we discovered elevated cell proliferation and invasion

Na+/H+ exchanger NHE1, a major determinant of intracellular pH (pHi) in mammalian central neurons, promotes neurite outgrowth under both basal and netrin-1-stimulated conditions. The small GTP binding proteins and their effectors have a dominant role in netrin-1-stimulated neurite outgrowth. Since NHE1 has been shown previously to work downstream of the Rho GTPases-mediated polarized membrane protrusion

LDL receptor-related proteins 6 (LRP6) is a type I transmembrane receptor (C-terminus in cytosol), which appears to be essential in numerous biological processes, since it is an essential co-receptor of Wnt ligands for canonical β-catenin dependent signal transduction. It was shown that tissue plasminogen activator (tPA), physically interacting with LRP6, induces protein phosphorylation, which may

Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti-CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs

The extracellular matrix microenvironment of adipose tissue is of critical importance for the differentiation, remodeling and function of adipocytes. Fibrillin-1 is one of the main components of microfibrils and a key player in this process. Furin processing of profibrillin-1 results in mature fibrillin-1 and releases the C-terminal propeptide as a circulating hunger hormone, asprosin. Mutations in

Basal Cell Carcinoma (BCC) represents the most common form of all cancers. BCC is characteristically surrounded by a fibromyxoid stroma. Previous studies have suggested a shift towards a Th2 response, an increase in T regulatory lymphocytes and the presence of cancer-associated fibroblasts in the BCC tumor microenvironment. In this study, we aimed to further characterize the BCC tumor microenvironment

Hypoxia refers to the decrease in oxygen tension in the tissues, and the central effector of the hypoxic response is the transcription factor Hypoxia-Inducible Factor α (HIF1-α). Transient hypoxia in acute events, such as exercising or regeneration after damage, play an important role in skeletal muscle physiology and homeostasis. However, sustained activation of hypoxic signaling is a feature of skeletal

Retinoblastoma (RB) is one of the most common ophthalmic tumors, and most of the patients have been identified as advanced at the time of diagnosis, which is directly related to high mortality. Recent studies showed that long noncoding RNA (lncRNA) and miRNAs play key roles in the development、progression、or treatment of cancer, such as RB. However, the role of lncRNA -TP73-AS1 in RB remains unclear

Previously, we reported that an extracellular matrix protein, osteopontin (OPN), is involved in various autoimmune diseases using a neutralizing polyclonal antibody against OPN generated in rabbits. However, the antibody cannot be used for long-term mouse models of chronic inflammatory disease because of the induction of antibodies against anti-OPN rabbit IgG. In this study, we generated a new antibody

It is widely believed that extracellular vesicles (EVs) mediate intercellular communications by functioning as messengers. EVs contain various biomolecules, including nucleic acids and proteins, as cargo in the internal space. Thus, it has been postulated that this cargo can be transferred from donor cells to recipient cells, leading to phenotypic changes in the recipient cells. However, there is a

Paracrine signaling between tumor and surrounding stromal cells is critical for the maintenance of tumor microenvironment during ovarian cancer progression. Small extracellular vesicles (sEVs; exosomes in particular) are nano-sized vesicles secreted actively by many cells including tumor cells and are found to have fundamental roles in intercellular communication through shuttling functional RNAs.

Pembrolizumab monotherapy has been demonstrated as a first-line therapy for non-small-cell lung cancer (NSCLC) patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%; however, the clinical efficacy is limited by the unreasonable threshold of the TPS. A recent study published by Mok et al. (Lancet 393:1819–1830, 2019) showed that pembrolizumab monotherapy could also be

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor prognosis. Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor and emerging evidence shows it is associated with tumor initiation and promotion. However, the relationship between AHR and ESCC is not clear and it is meaningful to explore whether AHR could be a therapeutic target. In

Epithelial tissues provide tissue barriers and specialize in organs and glands. When epithelial homeostasis is physiologically or pathologically stimulated, epithelial cells produce mesenchymal cells through the epithelial-mesenchymal transition, forming new tissues, promoting the cure of diseases or leading to illness. A variety of cytokines are involved in the regulation of epithelial cell differentiation

Skeletal muscle fibro-adipogenic progenitors (FAPs) are tissue-resident connective tissue cells and the main cellular source of pathological fibro-fatty scar associated with muscle disorders. Although our knowledge about skeletal muscle mesenchymal progenitor cells has exploded in the past decade, we still lack information about their origin, fate, gene regulation, function, and stemness. A recent

Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated T-helper (Th)1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through

Tobacco smoke’s harmful effects are well-known; the harmful effects of tobacco smoke have been well-investigated. Nicotine in tobacco smoke contributes to the pathogenesis of various conditions, such as lung cancer, coronary artery disease and asthma. A decade ago, a seemingly safer alternative to tobacco cigarettes was introduced- the E-cigarette. However, studies have found that E-cigarette smoke

Vascular Endothelial Growth Factor-A (VEGFA) signaling is crucial to the cellular processes involved in angiogenesis. Previously, we assembled a network of molecular reactions induced by VEGFA in human umbilical vein endothelial cell populations. Considering transcriptome as a read-out of the transcriptional and epigenomic regulatory network, we now present an analysis of VEGFA-induced temporal transcriptome

Diabetic retinopathy (DR) is a major cause of acquired blindness among working adults. The retinal pigment epithelium (RPE), constitutes an outer blood-retinal barrier, is vastly affected in diabetic humans and animals. Lower levels of lutein in the serum and retina of diabetic population, and beneficial effects of carotenoids supplementation in diabetic retinopathy patients created an interest to