Silencing NLRC5 inhibits extracellular matrix expression in keloid fibroblasts via inhibition of transforming growth factor-β1/Smad signaling pathway

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• 作者：Hai-Li Ma^a ; ^b ; Xue-Fu Zhao^b ; Guan-Zhi Chen^c ; Rong-Hui Fang^d ; ^{ronghuixa@163.com" class="auth_mail" title="E-mail the corresponding author} ; Fu-Ren Zhang^a ; ^e ; ^f ; ^g ; ^h ; ^{furenzhangskin@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NLRC5 ; Transforming growth factor-β1 (TGF-β1) ; Keloid fibroblasts (KFs) ; TGF-β1/Smad signaling
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：83
• 期：Complete
• 页码：1016-1021
• 全文大小：979 K

文摘

Dermal fibrosis is characterized by collagen accumulation and hyperproliferation of fibroblasts. NLRC5, as the largest member of nucleotide-binding domain and leucine-rich repeat (NLRs) family, has recently been implicated in the development of hepatic fibrosis. However, the role of NLRC5 in dermal fibrosis remains unknown. Therefore, herein, we investigated the effects of NLRC5 on keloid fibroblasts (KFs) and transforming growth factor-β1 (TGF-β1)-induced collagen expression and explored the underlying mechanism. We observed that NLRC5 mRNA and protein levels were highly expressed in KFs, silencing NLRC5 greatly suppressed TGF-β1-induced KFs proliferation. Silencing NLRC5 also obviously inhibited the expression of type I collagen, CTGF and α-smooth muscle actin (α-SMA) in human KFs induced by TGF-β1, as well as the expression of TGF-β receptor I and II. Furthermore, silencing NLRC5 suppressed the expression of TGF-β1-induced Smad2 and Smad3 phosphorylation in human KFs. Taken together, our study suggest that silencing NLRC5 reduced ECM expression in KFs through inhibiting the TGF-β1/Smad signaling pathway. Therefore, NLRC5 may represent a promising target for treatment of the keloid disease.