Smad interacting protein 1 influences transforming growth factor-β1/Smad signaling in extracellular matrix protein production and hypertrophic scar formation

被引：31

作者：

Fang, Xiaobing ^{[1
]}

Hu, Xiaolong ^{[1
]}

Zheng, Zhao ^{[1
]}

Tao, Ke ^{[1
]}

Wang, Hongtao ^{[1
]}

Guan, Hao ^{[1
]}

Shi, Jihong ^{[1
]}

Ji, Peng ^{[1
]}

Cai, Weixia ^{[1
]}

Bai, Xiaozhi ^{[1
]}

Zhu, Xiongxiang ^{[1
]}

Han, Juntao ^{[1
]}

Liu, Jiaqi ^{[1
]}

Hu, Dahai ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp, Dept Burns & Cutaneous Surg, 127 Changle West Rd, Xian 710032, Shaanxi, Peoples R China

来源：

JOURNAL OF MOLECULAR HISTOLOGY | 2019年 / 50卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Fibrosis; Hypertrophic scar; Smad; Smad interacting protein 1; Transforming growth factor-beta(1); FACTOR-BETA; COLLAGEN EXPRESSION; III COLLAGEN; FIBROBLASTS; FIBROSIS; MYOFIBROBLAST; MICRORNA-192; CONTRACTION; MECHANISMS; INHIBITION;

D O I：

10.1007/s10735-019-09844-w

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The transforming growth factor (TGF)-beta/Smad signal transduction pathway is closely associated with hypertrophic scar (HS) formation. Smad interacting protein 1 (SIP1) is a cytoplasmic protein that efficiently regulates Smad2-/3-dependent signaling within the TGF-beta(1) pathway. SIP1 influences collagen synthesis in the HS through a heretofore unknown mechanism. This study investigated the role of the SIP1-mediated TGF-beta(1)/Smad signaling pathway in extracellular matrix (ECM) protein production and hypertrophic scarring. SIP1 expression was markedly lower in HS vs. normal skin (NS) tissue, and alpha-smooth muscle actin (alpha-SMA) content and collagen I/III (Col I/III) synthesis were inversely correlated with SIP1 expression. Furthermore, SIP1 inhibited Smad2/3 phosphorylation in vitro, and improved the collagen-based architecture of the scar while reducing collagen expression and overall scar formation in a rabbit ear model of HS. Based on these findings, we propose that SIP1 acts as a molecular modulator capable of altering Smad2-/3-facilitated signaling through the control of Smad phosphorylation, thus inhibiting alpha-SMA and collagen upregulation in fibroblasts and, ultimately, HS formation. The low SIP1 content in scar tissue also suggests that SIP1 (and positive regulation thereof) is a prospective target for selective HS drug therapy.

引用

页码：503 / 514

页数：12

共 55 条

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