Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China; Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China; Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, China.
J Dig Dis. 2014 Apr;15(4):202-10. doi: 10.1111/1751-2980.12126.
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.
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)-β1 was studied by immunohistochemistry and Western blot in C57BL/6 wild-type mice treated with recombinant IGFBP-rP1 (rIGFBP-rP1).
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-β1 in rIGFBP-rP1-treated mice.
IGFBP-rP1 contributes to the development of liver fibrosis and may be a novel molecule involved in the progression of hepatic fibrogenesis.
本研究旨在探讨胰岛素样生长因子结合蛋白相关蛋白 1（IGFBP-rP1）在实验性疾病模型和人类肝组织样本中肝纤维化发展中的作用。
通过免疫组织化学法检测 IGFBP-rP1 在纤维化和肝硬化人类肝组织标本中的细胞分布模式。通过小干扰 RNA（siRNA）对培养的肝星状细胞（HSCs）进行 IGFBP-rP1 的基因沉默，并通过定量实时聚合酶链反应（PCR）和 Western blot 测定沉默效果。我们还通过 Western blot 测定了 siRNA 介导的 IGFBP-rP1 基因沉默对细胞外基质（ECM）成分产生的影响。通过免疫组织化学和 Western blot 研究了重组 IGFBP-rP1（rIGFBP-rP1）处理的 C57BL/6 野生型小鼠中 ECM 成分和转化生长因子（TGF）-β1 的表达。
IGFBP-rP1 在纤维化和肝硬化的人类肝组织标本中表达显著上调，这种增加与观察到的胶原纤维数量呈正相关。IGFBP-rP1 的 siRNA 介导的基因沉默导致 HSCs 中胶原 I 和纤维连接蛋白的水平显著降低。此外，IGFBP-rP1 过表达可显著增加 rIGFBP-rP1 处理的小鼠中胶原、纤维连接蛋白和 TGF-β1 的产生。
IGFBP-rP1 有助于肝纤维化的发展，可能是肝纤维化进展中涉及的新分子。
