Accumulation of versican facilitates wound healing: implication of its initial ADAMTS-cleavage site.

Accumulation of versican facilitates wound healing: implication of its initial ADAMTS-cleavage site. Matrix Biol. 2019 Oct 26;: Authors: Islam S, Chuensirikulchai K, Khummuang S, Keratibumrungpong T, Kongtawelert P, Kasinrerk W, Hatano S, Nagamachi A, Honda H, Watanabe H Abstract Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan in the extracellular matrix, and is expressed at high levels in tissues during development and remodeling in pathological conditions. Its core protein is cleaved at a region close to the N-terminal end of CSβ domain by several members of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, i.e., ADAMTS-1, 4, 5, 9, 15, and 20. Here, using a CRISPR/Cas9 system, we generated knock-in mice (V1R), which express an ADAMTS cleavage-resistant versican. Some V1R homozygote mice, termed R/R, exhibit syndactyly and organ hemorrhage. In wound healing experiments, R/R wound shows accumulation of versican and activated TGFβ-signaling in the early stage, leading to faster healing than wild type wound. Immunostaining for Ki67, CD31, smooth muscle α-actin, periostin demonstrates higher levels of overall cell proliferation and an increased number of endothelial cells and myofibroblasts. Immunostaining for CD11b and qRT-PCR for macrophage markers revealed increased levels of inflammatory cell infiltration, especially those of M1 macrophages. Cultured R/R dermal fibroblasts revea...
Source: Matrix Biology - Category: Molecular Biology Authors: Tags: Matrix Biol Source Type: research