Insulin-like growth factor binding protein-related protein 1 contributes to hepatic fibrogenesis

被引：51

作者：

Guo, Xiao Hong ^{[1
,2
,3
]}

Liu, Li Xin ^{[1
,2
,3
]}

Zhang, Hai Yan ^{[1
,2
,3
]}

Zhang, Qian Qian ^{[1
,2
,3
]}

Li, Yuan ^{[1
]}

Tian, Xiao Xia ^{[1
]}

Qiu, Zhi Hong ^{[1
]}

机构：

[1] Shanxi Med Univ, Clin Hosp 1, Dept Gastroenterol & Hepatol, Taiyuan 030001, Shanxi Province, Peoples R China

[2] Shanxi Med Univ, Clin Hosp 1, Expt Ctr Sci & Res, Taiyuan 030001, Shanxi Province, Peoples R China

[3] Shanxi Med Univ, Prov Dept, Key Lab Cell Physiol, Minist Educ, Taiyuan 030001, Shanxi Province, Peoples R China

来源：

JOURNAL OF DIGESTIVE DISEASES | 2014年 / 15卷 / 04期

基金：

中国国家自然科学基金;

关键词：

hepatic stellate cells; hepatic fibrosis; insulin-like growth factor binding protein-related protein 1; transforming growth factor beta 1; extracellular matrix; VASCULAR ENDOTHELIAL-CELLS; LIVER FIBROSIS; STELLATE CELLS; COLORECTAL-CANCER; BREAST-CANCER; LUNG-CANCER; IGFBP-RP1; ACTIVATION; MECHANISMS; DISEASE;

D O I：

10.1111/1751-2980.12126

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Objective The aim of this study was to investigate the role of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) in the development of hepatic fibrogenesis in experimental disease models and human liver samples. Methods Cellular distribution patterns of IGFBP-rP1 were assessed by immunohistochemistry in fibrotic and cirrhotic human liver specimens. Gene silencing of IGFBP-rP1 was performed on cultured hepatic stellate cells (HSCs) by small interfering RNA (siRNA), and the silencing effect was determined by quantitative real-time polymerase chain reaction (PCR) and Western blot. We also determined the effects of siRNA-mediated gene silencing of IGFBP-rP1 on the production of extracellular matrix (ECM) components by Western blot. The expression of ECM components and transforming growth factor (TGF)-beta 1 was studied by immunohistochemistry and Western blot in C57BL/6 wild-type mice treated with recombinant IGFBP-rP1 (rIGFBP-rP1). Results Expression of IGFBP-rP1 was significantly elevated in fibrotic and cirrhotic human liver specimens, and this increase was positively correlated with the number of collagen fibers observed. siRNA-mediated gene silencing of IGFBP-rP1 resulted in significantly decreased levels of collagen I and fibronectin in HSCs. Moreover, IGFBP-rP1 overexpression significantly increased the production of collagen, fibronectin and TGF-beta 1 in rIGFBP-rP1-treated mice. Conclusions IGFBP-rP1 contributes to the development of liver fibrosis and may be a novel molecule involved in the progression of hepatic fibrogenesis.

引用

页码：202 / 210

页数：9

共 42 条

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