Type V Collagen in Health, Disease, and Fibrosis

Abstract

Type V collagen (COLV) is a regulatory fibril-forming collagen. It has at least three different molecular isoforms-a1(V) 2 a2(V), a1(V) 3, and a1(V)a2(V)a3(V)-formed by combinations of three different polypeptide a chains-a1(V), a2(V), and a3(V). COL V is a relatively minor collagen of the extracellular matrix (ECM). Morphologically, COLV occurs as heterotypic fibrils with type I collagen (COLI), microfilaments, or 12-nm-thick fibrils. COLV is synthesized in various mesenchymal cells and its gene expression is modulated by TGF-b and growth factors. While resistant to digestion by interstitial collagenases, native and denatured COLV are degraded by metalloproteinases and gelatinases, thereby promoting ECM remodeling. COLV interacts with matrix collagens and structural proteins, conferring structural integrity to tissue scaffolds. It binds matrix macromolecules, modulating cellular behavior, and functions. COLV coassembles with COLI into heterotypic fibrils in the cornea and skin dermis, acting as a dominant regulator of collagen fibrillogenesis. COLV deficiency is associated with loss of corneal transparency and classic EhlersDanlos syndrome, while COLV overexpression is found in cancer, granulation tissue, inflammation, atherosclerosis, and fibrosis of lungs, skin, kidneys, adipose tissue, and liver. COLV isoform containing the a3(V) chain is involved in mediating pancreatic islet cell functions. In the liver, COLV is a minor but regular component of the ECM. Increases in COLV are associated with both early and advanced hepatic fibrosis. The neoepitopes of COLV have been shown to be a useful noninvasive serum biomarker for assessing fibrotic progression and resolution in experimental hepatic fibrosis. COLV is multifunctional in health, disease, and fibrosis. Anat Rec, 299:613-629, 2016. V C 2016 Wiley Periodicals, Inc.Key words: collagen V synthesis and degradation; collagen V deficiency and overexpression; collagen V in disease and fibrosis; collagen V neoepitopes; hepatic fibrosis biomarker

Basement Membrane Type IV Collagen and Laminin: An Overview of Their Biology and Value as Fibrosis Biomarkers of Liver Disease

“…It is known that a highly regulated equilibrium between synthesis and degradation of ECM proteins is required to achieve tissue homeostasis. An interruption of this equilibrium is regarded as the basis of pathological process, fibrosis included (Mak et al, ). MMPs are critical mediators of ECM remodeling and their expression is upregulated in liver fibrogenesis (Iredale et al, ).…”

Basement membranes and autoimmune diseases

“…In healthy lung, Col-V is a minor collagen component, expressed in intralveolar septa and walls of bronchi, terminal bronchioles, and blood vessels. Col-V is co-expressed with collagen I (Col-I), with which it co-assembles into heterotypic Col-I/V fibrils [135]; both are markedly increased in fibrotic lungs. Kα1T is produced in airway epithelial cells.…”

Proteomic Analysis Reveals a New Benefit of Periodic Mechanical Stress on Chondrocytes

“…Not only was type I collagen reduced, but type III, type V, type VI and other related collagens which are closely connected to fibrosis were also decreased after periodic mechanical stress. Among these, type V and type VI collagen serve as reservoirs for fibrogenic-related molecules and thus regulate the availability for fibrogenesis and fibrolysis [32]. However, many of the pathways that are relevant to these mechanisms rely on PTMs such as phosphorylation and not just on quantitative changes in protein levels [13, 14], so we had no idea how to explain the changes occurring during periodic mechanical stress until we performed the phosphoproteomic analysis.…”