RRC ID 48797
Author Horigome T, Takumi S, Shirai K, Kido T, Hagiwara-Chatani N, Nakashima A, Adachi N, Yano H, Hirai Y.
Title Sulfated glycosaminoglycans and non-classically secreted proteins, basic FGF and epimorphin, coordinately regulate TGF-β-induced cell behaviors of human scar dermal fibroblasts.
Journal J Dermatol Sci
Abstract BACKGROUND:Upon skin injuries, dermal fibroblasts actively produce transforming growth factor-β (TGF-β), which leads to the formation of α-smooth muscle actin (αSMA)-positive granulation tissues. The hyperplasia or incomplete regression of these tissues subsequently causes scar formation in the skin, where sulfated glycosaminoglycans (GAGs), side chains of unique proteoglycans, are supposed to play important roles.
OBJECTIVE:The aim of this study is to clarify the effects of sulfated GAGs on dermal cell behaviors triggered by the TGF-β signaling, along with its possible regulators basic fibroblast growth factor (bFGF) and cell surface epimorphin. bFGF and epimorphin might regulate the TGF-β-induced αSMA expression, they could exert such effects only in specific cellular contexts, given that they lack conventional signal sequences for extracellular localization.
METHODS:Human scar-derived dermal fibroblasts (HSFs) were treated with TGF-β alone, TGF-β plus bFGF, and TGF-β plus cell surface expression of epimorphin. The effects of GAGs on the expression of αSMA and the cellular morphology were then investigated.
RESULTS:A highly sulfated chondroitin sulfate (CS-E) or its substitute (heparinoid) had marked inhibitory effects on TGF-β-mediated changes in HSF behaviors. We found that heparinoid can directly associate with TGF-β, bFGF and epimorphin. We also found that bFGF downregulated αSMA, which was attenuated by heparinoid, whereas epimorphin augmented αSMA expression, which was further amplified by heparinoid.
CONCLUSIONS:TGF-β, bFGF and epimorphin in the extracellular microenvironment cooperatively affect HSF behaviors under the control of a highly sulfated chondroitin sulfate. These results provide important evidence towards understanding the regulation of TGF-β-induced HSF behaviors.
Volume 86(2)
Pages 132-141
Published 2017-5-1
DOI 10.1016/j.jdermsci.2017.01.014
PII S0923-1811(16)30953-7
PMID 28209294
MeSH Actins / metabolism Animals COS Cells Cell Membrane / metabolism Chlorocebus aethiops Chondroitin Sulfates / chemistry Cicatrix / metabolism* Fibroblast Growth Factor 2 / pharmacology Fibroblasts / metabolism* Glycosaminoglycans / chemistry* Heparinoids / metabolism Humans Proteoglycans / metabolism* Recombinant Proteins / pharmacology Signal Transduction Swine Syntaxin 1 / metabolism* Transforming Growth Factor beta / pharmacology*
IF 3.681
Times Cited 3
DNA material Genome Network Project Human cDNA IRAK027E21 (HGX010917) NRCD Human cDNA Are17H05 (HKR046973).