Keloid is a pathologic fibro-proliferative disorder and is characterized by hyper-proliferation of fibroblasts and excess extracellular matrix (ECM) deposition. Interferon regulatory factor 3 (IRF3) is a member of the interferon-regulatory factor (IRF) family and has been shown to play a critical modulator in the progression of fibrosis. However, the function of IRF3 in dermal fibrosis remains unclear. Thus, in this study, we investigated the effects of IRF3 on keloid-derived fibroblasts (KFs) proliferation and ECM expression, and explored the underlying mechanism. Our results indicated that the expression of IRF3 was highly expressed in human keloid tissues. Down-regulation of IRF3 significantly inhibited KF proliferation and the expression of type I collagen and α-smooth muscle actin (α-SMA), as well as suppressed the expression of TGF-β receptor I and II in TGF-β1-stimulated KFs. Furthermore, down-regulation of IRF3 suppressed the phosphorylation levels of Smad2 and Smad3 in human KFs induced by TGF-β1. Taken together, our data showed that down-regulation of IRF3 inhibited the proliferation and ECM expression in KFs via suppressing the TGF-β1/Smad signaling pathway. Thus, our findings suggest that IRF3 may represent a promising target for treatment of the keloid disease.
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