title: [Evidence for retinoic acid modulating expression of cyclin-dependent kinase inhibitors in rat hepatic stellate cells].
abstract: OBJECTIVE
  To study the effects of retinoic acid on regulation of expressions of cyclin-dependent kinase inhibitors, i.e. p16, p21 and p27 in cultured rat hepatic stellate cells.
  
  
  METHODS
  Stellate cells were isolated from healthy rat livers and cultured. After stimulated with 1 ng/ml transforming growth factor beta 1, subcultured hepatic stellate cells were treated with or without 1 nmol/ml retinoic acid. MTT assay, immunocytochemistry for p16, p21, p27 and alpha-smooth muscle actin protein, in situ hybridization for retinoic acid receptor beta 2 and p16, p21 and p27 mRNA and quantitative image analysis (partially) were performed.
  
  
  RESULTS
  Retinoic acid markedly inhibited hepatic stellate cells proliferation (41.50%, P<0.05), decreased the protein level of alpha-smooth muscle actin (55.09%, P<0.05), and induced hepatic stellate cells to express retinoic acid receptor beta 2 mRNA. In addition, retinoic acid increased the protein level of p16 (218.75%, P <0.05) and induced p21 protein expression; meanwhile, p27 was undetectable by immunocytochemistry in both control and retinoic acid-treated hepatic stellate cells. However, retinoic acid had no influence on the mRNA level of p16, p21 or p27 as determined by in situ hybridization.
  
  
  CONCLUSIONS
  Up-regulation of p16 and p21 on post-transcriptional level may contribute, in part, to retinoic acid inhibition of transforming growth factor beta 1-initiated rat hepatic stellate cells activation in vitro.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1; D014212:Tretinoin / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
chemical_list: C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta; D050760:Cyclin-Dependent Kinase Inhibitor p27; D014212:Tretinoin; D018844:Cyclin-Dependent Kinases