Biologie de la peau

Decorin/decorin

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Decorin belongs to the family of small leucine-rich proteoglycans that harbors one chondroitin/dermatan sulfate side chain at its N terminus. It was originally named because of its ability to “decorate” collagen fibrils, thereby regulating fibrillogenesis, a key mechanism of matrix assembly and homeostasis. Decorin binds to type I collagen and stabilizes the structure of the extracellular matrix. Decorin interacts also with fibronectin, thrombospondin and the complement component C1q.

It suppresses cellular proliferation, is strongly expressed in quiescent post-confluent fibroblasts and rarely expressed within actively proliferating or transformed tissues.

Decorin contains leucine-rich repeats (=matrikines) able to bind EGF receptor (Kd 27-887 nM), thereby triggering a signaling cascade that initially leads to phosphorylation of mitogen-activated protein (MAP) kinase, induction of p21, and growth suppression. This activation eventually results in a decrease of EGFR levels and nearly complete suppression of EGFR autophosporylation.

Decorin regulates the TGF-β signaling pathway. Decorin suppresses tumor cell–mediated angiogenesis by inhibiting the endogenous production of vascular endothelial cell growth factor. Decorin binds directly and with high affinity (Kd = 1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF) and suppresses intracellular levels of β-catenin, a known downstream Met effector, and thereby inhibits Met-mediated cell migration and growth.

During skin repair, decorin would function as a quiescence signal inducing decrease of migration, proliferation and extracellular matrix production by fibroblasts when the wound has reached its mature state.

Bibliography

Decorin Wikipedia

Csordás G, Santra M, Reed CC, Eichstetter I, McQuillan DJ, Gross D, Nugent MA, Hajnóczky G, Iozzo RV. Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo. J Biol Chem. 2000 Oct 20 ;275(42):32879-87.

Goldoni S, Humphries A, Nyström A, Sattar S, Owens RT, McQuillan DJ, Ireton K, Iozzo RV. Decorin is a novel antagonistic ligand of the Met receptor. J Cell Biol. 2009 May 18 ;185(4):743-54.

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