The turnover and degradation of collagen.
The interstitial collagens are degraded predominantly extracellularly, by specific collagenases (metalloproteinases) capable of cleaving the helical region across the three chains at a similar locus, solubilizing the cleaved products from the fibril. Other neutral proteinases may also function in this role by cleaving near cross-links in the fibril. Collagen type, molecular aggregation and small changes in temperature all markedly affect rates of collagenolysis in the fibril. Regulation of collagenolysis is also modulated at the levels of (1) cellular production of latent collagenase (procollagenase), (2) activation of latent collagenase, and (3) production of collagenase inhibitors. Fibroblastic cells and certain macrophages are probably the predominant sources of collagenases in inflammation; an enzyme in polymorphonuclear leucocytes (neutrophils) is distinct from the tissue enzyme. Molecules such as mononuclear cell factor (MCF), homologous with interleukin 1, which augment cellular collagenase production in inflammation, are derived from monocytes. The mechanisms of augmented collagenase production involve new protein synthesis and, if this augmentation is analogous to that produced by urate crystals, it is probably associated with increased levels of procollagenase mRNA. MCF production is itself controlled by products of lymphocytes as well as by interactions of monocytes with the Fc portion of immunoglobulins and components of the extracellular matrix. Activation of latent (pro)collagenase probably occurs in vivo through the action of neutral proteinases such as plasmin (through plasminogen activator). These effects may be indirect and exerted through proteolytic activation of a procollagenase activator. Tissue inhibitors act to regulate the active collagenase.
D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D003012:Microbial Collagenase / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D003094:Collagen; D003012:Microbial Collagenase