title: Raf Kinase Inhibitory Protein Down-Expression Exacerbates Hepatic Fibrosis In Vivo and In Vitro.
abstract: OBJECTIVE
  Raf kinase inhibitory protein (RKIP) is closely associated with numerous tumors and participates in their development through regulating the growth, apoptosis, invasion and metastasis of tumor cells. However, the role of RKIP in chronic liver injury and particularly in liver fibrosis is still unclear.
  
  
  METHODS
  In the present study, hepatic fibrosis was induced by porcine serum (PS) in rats and primary hepatic stellate cells (HSCs) were isolated from rat livers. Moreover, locostatin was used to interfere with RKIP expression.
  
  
  RESULTS
  RKIP expression was significantly inhibited by locostatin in both liver tissues of rats and primary HSCs. Down-regulating RKIP expression resulted in serious liver injury, extensive accumulation of collagen, and significant increase in the levels of ALT, AST and TNF-α during liver fibrosis in rats. Moreover, down-regulating RKIP significantly promoted HSCs proliferation and colony formation in vitro. Reduced RKIP significantly increased the production of collagen and the level of α-SMA as well as the expression of MMP-1 and MMP-2 in both liver tissues and primary HSCs. Furthermore, down-regulating RKIP promoted the activation of the ERK and TLR4 signaling pathways.
  
  
  CONCLUSIONS
  Our findings clearly indicate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. The decrease in RKIP expression may exacerbate chronic liver injury and liver fibrosis.
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China.
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
authors.forename: Chunhong
authors.initials: C
authors.lastname: Liang
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Jinlan
authors.initials: J
authors.lastname: Nie
authors.forename: Shengjuan
authors.initials: S
authors.lastname: Lu
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Lu
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
authors.forename: Zhongpeng
authors.initials: Z
authors.lastname: Lu
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; C550693:PEBP1 protein, rat; D049488:Phosphatidylethanolamine Binding Protein; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1