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Type VI Collagen: Its Biology and Value as a Biomarker of Hepatic Fibrosis

Journal: Austin Biomarkers & Diagnosis (Vol.1, No. 2)

Publication Date:

Authors : ; ; ;

Page : 1-9

Keywords : Filamentous Type VI collagen; Soluble collagen VI; Collagen VI assembly; Matrix metalloproeteinase; Biomarkers of liver fibrogenesis; Hepatic stellate cells;

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Collagen VI forms a filamentous network in connective tissue, linking matrix macromolecules and cells. It is composed of three chains, α1(VI), α2(VI), and α3(VI), with a globular domain at each end. Additionally, three novel chains α4, α5, and α6 were identified. Intracellularly, collagen VI monomers dimerize and form tetramers, which are secreted and associate into microfilaments extracellularly. Collagen VI gene expression is regulated differently than I or III. Collagen VI interacts with fibronectin, mediates cell adhesion and promotes migration. Soluble collagen VI acts as a sensor for tissue damage, modulating mesenchymal cell proliferation and survival, matrix homeostasis, and wound healing. Three collagen VI-deficient mouse models have been generated, which have been used to investigate collagen VI-related myopathies, mammary carcinogenesis, and skeletal muscle satellite cell homeostasis. Collagen VI is upregulated in fibrosis of liver, skin, kidneys, lungs, heart, and adipose tissue. In the liver, collagen VI normally accounts for 0.1% of total collagen, but is increased 10-fold in cirrhosis. Elevated soluble collagen VI in circulation is considered an early biomarker of alcoholic liver fibrosis. Collagen VI immunostaining is enhanced in fibrotic foci, co-distributing with collagens I, III and V. Hepatic stellate cells (HSCs) are likely the source of perisinusoidal collagen VI. The α2(VI) chain sequesters hepatic matrix metalloproteinase (MMP)-1, -3, and -8 and blocks the enzymes' activation, preventing fibrolysis. CO6-MMP, a collagen VI fragment generated by MMP-2 and -9, is a specific biomarker of collagen VI degradation in experimental liver fibrogenesis. The collagen VI receptor on HSCs offers selective targets for anti-fibrotic agents.

Last modified: 2016-10-26 14:38:12