Pro-fibrotic phenotype of human skin fibroblasts induced by periostin via modulating TGF-β signaling

Publication date: Available online 6 February 2018
Source:Journal of Dermatological Science
Author(s): Miwa Kanaoka, Yukie Yamaguchi, Noriko Komitsu, Carol A. Feghali-Bostwick, Masahiro Ogawa, Kazuhiko Arima, Kenji Izuhara, Michiko Aihara
BackgroundPeriostin is a matricellular protein that belongs to a class of extracellular matrix (ECM)-related molecules defined by their ability to modulate cell–matrix interactions. We previously reported an elevated level of circulating periostin in patients with systemic sclerosis (SSc) and its association with the severity of skin sclerosis.ObjectiveTo examine the role of periostin in transforming growth factor (TGF)-β signaling involved in fibrosis.MethodsLevels of periostin were examined in skin and lung fibroblasts obtained from SSc patients. Levels of ECM proteins and pro-fibrotic factors were evaluated in periostin-expressing human skin fibroblasts in the presence or absence of TGF-β. Effects of periostin on the Smad proteins were also evaluated following stimulation with TGF-β by immunoblotting, immunofluorescence staining, and RNA interference.ResultsPeriostin was strongly expressed in skin and lung fibroblasts from SSc patients. Although recombinant periostin alone did not affect ECM protein levels, TGF-β and recombinant periostin treatment or periostin overexpression in skin fibroblasts significantly enhanced the production of ECM proteins. Overexpression of periostin in the presence of TGF-β also augmented expressions of α-smooth muscle actin and early growth response-1 but decreased the level and activity of matrix metalloproteinase 1. Interestingly, the level of Smad 7, a TGF-β-inducible inhibitor of TGF-β signaling, was reduced in periostin-expressing fibroblasts but increased in periostin-silenced fibroblasts. In addition, Smad 7 reduction induced by periostin was partially inhibited in integrin αV-silenced fibroblasts.ConclusionPeriostin contributes to fibrosis by enhancing TGF-β signaling via Smad 7 inhibition, which may lead to ECM deposition and periostin generation.



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