期刊
JOURNAL OF DERMATOLOGICAL SCIENCE
卷 90, 期 2, 页码 199-208出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2018.02.001
关键词
Periostin; Fibrosis; Systemic sclerosis; Smad proteins
类别
资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology
Background: Periostin 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. Objective: To examine the role of periostin in transforming growth factor (TGF)-beta signaling involved in fibrosis. Methods: Levels 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-beta. Effects of periostin on the Smad proteins were also evaluated following stimulation with TGF-beta by immunoblotting, immunofluorescence staining, and RNA interference. Results: Periostin was strongly expressed in skin and lung fibroblasts from SSc patients. Although recombinant periostin alone did not affect ECM protein levels, TGF-beta 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-beta also augmented expressions of a-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-beta-inducible inhibitor of TGF-beta signaling, was reduced in periostinexpressing fibroblasts but increased in periostin-silenced fibroblasts. In addition, Smad 7 reduction induced by periostin was partially inhibited in integrin alpha(v)-silenced fibroblasts. Conclusion: Periostin contributes to fibrosis by enhancing TGF-beta signaling via Smad 7 inhibition, which may lead to ECM deposition and periostin generation. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
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