title: Insulin-like growth factor binding protein-related protein 1 contributes to hepatic fibrogenesis.
abstract: 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)-β1 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-β1 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.
authors.affiliation: 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.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Guo
authors.forename: Li Xin
authors.initials: LX
authors.lastname: Liu
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Zhang
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiao Xia
authors.initials: XX
authors.lastname: Tian
authors.forename: Zhi Hong
authors.initials: ZH
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; C102529:insulin-like growth factor binding protein-related protein 1
keywords: extracellular matrix; hepatic fibrosis; hepatic stellate cells; insulin-like growth factor binding protein-related protein 1; transforming growth factor β1