title: Inhibition of Focal Adhesion Kinase on Hepatic Stellate-cell Adhesion and Migration.
abstract: OBJECTIVE
  Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K) signals participate in the activation of HSCs. We evaluated the effect of FAK-related nonkinase (FRNK) on the adhesion and migration of HSCs.
  
  
  METHODS
  Hepatic fibrosis was induced in Sprague-Dawley rats by means of bile duct ligation. Livers were harvested at 1, 2, 3 and 4 weeks after the ligation; livers of sham-operated animals were harvested at 4 weeks after ligation. Histopathologic features were evaluated in liver sections stained with hematoxylin-eosin and Sirius Red stain. HSCs were transfected with FRNK plasmid. The adhesion of HSCs was examined with a toluidine blue colorimetric assay. The migration of HSCs was evaluated by the use of an improved Boyden double-chamber method. Protein and messenger RNA levels in the liver and the HSCs were determined by Western blot analysis and real-time polymerase chain reaction, respectively.
  
  
  RESULTS
  Hematoxylin-eosin staining of the liver documented the presence of fibrosis in the rats. Actin and PI3K expression was increased in parallel with the development of hepatic fibrosis. At the same time, activator protein-1 (AP-1) (c-fos, c-jun) mRNA in the livers was increased. Overexpression of FRNK inhibited the adhesion and migration of HSCs time-dependently. Simultaneously, FRNK inhibited PI3K mRNA and protein expression and c-jun mRNA expression.
  
  
  CONCLUSIONS
  FRNK inhibited the adhesion and migration of HSCs by decreasing the expressions of the FAK-PI3K-AP-1 signal pathway.
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, Hebei Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, Hebei Province, China.
authors.forename: Junji
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, Hebei Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, Hebei Province, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, Hebei Province, China. Electronic address: jianghuiqing1959@sina.com.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000502:physiology*; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000235:genetics
chemical_list: D000199:Actins; D005353:Fibronectins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C113183:FAK-related nonkinase; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat
keywords: Adhesion; Focal adhesion kinase–related nonkinase; Hepatic stellate cells; Migration; Phosphatidylinositol 3-kinase