Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: Systemic sclerosis (SSc) results in significant morbidity and mortality due to organ fibrosis characterized by increased deposition of extracellular matrix (ECM). Periostin is one of the matricellular proteins, a class of ECM-related molecules defined by their ability to modulate cell–matrix interactions. Recent studies revealed that periostin serves as a critical regulator of wound healing, epithelial mesenchymal transition, and fibrosis. We previously reported elevated serum periostin levels in SSc patients which correlated with severity of skin sclerosis. However, the pathogenic role of periostin in fibrosis has not been well elucidated. In this study, we further examined the role of periostin on transforming growth factor-β (TGF-β) signaling mediating fibrosis.
Methods: Periostin levels in skin and lung primary fibroblasts obtained from SSc patients were first determined. To enhance the function of periostin, we overexpressed periostin in human skin fibroblasts and examined protein levels of ECM proteins, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) in the presence or absence of TGF-β by immunoblotting. Interaction of periostin with TGF-β receptors (TGF-βRI, TGF-βRII) was assessed by immunoprecipitation assay. Furthermore, effects of periostin to Smad proteins following TGF-β stimulation were also evaluated.
Results: Periostin was strongly expressed in skin and lung primary fibroblasts obtained from SSc patients compared with healthy subjects. Although single stimulation of recombinant periostin (rP) did not increase ECM protein levels, rP-treated fibroblasts and periostin overexpressed fibroblasts produced significant ECM proteins in the presence of TGF-β compared to respective control fibroblasts stimulated with TGF-β alone. Overexpression of periostin enhanced the induction of α-SMA in the presence of TGF-β and increased expression of MMP-1, which is reported to associate TGF-β activation. In addition, phosphorylation of Smad 2/3 by TGF-β was not affected by periostin, but a level of Smad 7, a TGF-β-inducible inhibitor of TGF-β signaling, was reduced in periostin expressed fibroblasts stimulated with TGF-β.
Conclusion: Periostin may contribute to fibrosis by enhancing TGF-β signaling via TGF-β activation and Smad 7 inhibition, which leads to further ECM deposition and periostin generation. Periostin may be a therapeutical target molecule mediating fibrosis.
Disclosure:
Y. Yamaguchi,
None;
N. Koumitsu,
None;
K. Arima,
None;
K. Izuhara,
None;
M. Aihara,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/periostin-may-promote-productin-of-extracellular-matrix-by-modulating-tgf-%ce%b2-signaling-in-human-skin-fibroblasts/