Research ArticleFibrosis

Thrombospondin-1 promotes matrix homeostasis by interacting with collagen and lysyl oxidase precursors and collagen cross-linking sites

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Science Signaling  29 May 2018:
Vol. 11, Issue 532, eaar2566
DOI: 10.1126/scisignal.aar2566

Thrombospondin-1 controls collagen homeostasis directly

Collagens, components of the extracellular matrix important for tissue architecture and function, undergo a complex series of processing events before and after secretion. Deposition of excessive amounts of collagens and abnormal cross-linking of collagen fibrils are associated with fibrosis. Using knockout mice, primary human dermal fibroblasts, and in vitro binding assays, Rosini et al. found that thrombospondin-1 (TSP1) bound to and inhibited the processing of the precursor form of the collagen cross-linking enzyme lysyl oxidase. TSP1 also bound to collagen molecules intracellularly and at conserved cross-linking sites. Blocking the latter interaction extracellularly stimulated fibroblasts to undergo inappropriate conversion to myofibroblasts. Although the mechanism by which the TSP1-collagen interaction prevents fibroblast-to-myofibroblast conversion is unclear, these findings identify a direct role for TSP1 as a modulator of the collagen matrix.

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