Therapeutic Potential of Targeting Periostin in the Treatment of Graves’ Orbitopathy

Abstract

Periostin is a matricellular protein that is ubiquitously expressed in normal human tissues and is involved in pathologic mechanism of chronic inflammatory and fibrotic disease. In this study we investigate periostin in the pathogenesis of Graves’ orbitopathy (GO) using human orbital adipose tissue obtained from surgery and primary cultured orbital fibroblasts in vitro. POSTN (gene encoding periostin) expression in Graves’ orbital tissues and healthy control tissues was studied, and the role of periostin in GO pathologic mechanism was examined through small-interfering RNA (siRNA)-mediated silencing. POSTN gene expression was significantly higher in Graves’ orbital tissues than healthy control tissues in real-time PCR results, and immunohistochemical staining revealed higher expression of periostin in Graves’ orbital tissues than normal tissues. Silencing periostin using siRNA transfection significantly attenuated TGF-β-induced profibrotic protein production and phosphorylated p38 and SMAD protein production. Knockdown of periostin inhibited interleukin-1 β -induced proinflammatory cytokines production as well as phosphorylation of NF-κB and Ak signaling protein. Adipocyte differentiation was also suppressed in periostin-targeting siRNA transfected GO cells. We hypothesize that periostin contributes to the pathogenic process of inflammation, fibrosis and adipogenesis of GO. Our study provides in vitro evidence that periostin may be a novel potential therapeutic target for the treatment of GO.

Periostin increased by mechanical stress upregulates interleukin‐6 expression in the ligamentum flavum

“…41 Similarly, periostin knockdown decreased the expression of αSMA and Col1a1 in fibroblasts treated with TGF-β1. 30,42 On the other hand, some reports indicate that administration of periostin increases αSMA expression in fibroblasts, 43 while in other studies, periostin administration had no effect on αSMA expression in fibroblasts, 30,44 and a certain consensus has not been reached. The present study showed that FFSS-induced gene expression of both α-SMA and Col1a1 was suppressed by periostin knockdown, while periostin treatment did not increase the expression of these genes.…”

“…Periostin knockout mice showed decreased αSMA and Col1a1 expression in in vivo models of scleroderma 30 and palatal wounds 41 . Similarly, periostin knockdown decreased the expression of αSMA and Col1a1 in fibroblasts treated with TGF‐β1 30,42 . On the other hand, some reports indicate that administration of periostin increases αSMA expression in fibroblasts, 43 while in other studies, periostin administration had no effect on αSMA expression in fibroblasts, 30,44 and a certain consensus has not been reached.…”