title: Imatinib mesylate improves liver regeneration and attenuates liver fibrogenesis in CCL4-treated mice.
abstract: BACKGROUND
  Imatinib mesylate (STI-571), a tyrosine kinase inhibitor, has previously been demonstrated to attenuate liver fibrogenesis through inhibition of the activation of hepatic stellate cells (HSCs) in CCL(4)-treated rat models.
  
  
  OBJECTIVE
  This study aimed to further evaluate the role of STI-571 in liver regeneration.
  
  
  METHODS
  All animals were divided into four groups, and mice were treated with or without CCL(4) and STI-571 (n = 6 for each group).
  
  
  RESULTS
  Activated cultured HSCs in vitro with STI-571 administration showed increased apoptosis and reduced proliferation, as determined by flow cytometric analysis, 3-(4, 5-cimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, and confocal microscopy. STI-571 treatment attenuated liver fibrosis in vivo, as was evident in the results of histology, mRNA level, and expression analysis of smooth muscle actin and type I collagen. Mice treated with STI-571 had increased liver weight ratio and the improvement in liver regeneration was compatible with the change of serum interleukin 6 levels (p < 0.05). Further, increased apoptosis and a reduced proliferation were observed in the CCL(4)-treated mice after STI-571 treatment based on the immunohistochemical staining of Annexin V, phosphorylated STAT3, and PCNA.
  
  
  CONCLUSIONS
  STI-571 treatment effectively attenuated liver fibrogenesis and improved in liver regeneration in vivo and induced apoptosis in HSCs both in vitro and in vivo.
authors: Department of Surgery, Chang Gung Memorial Hospital and Medical School of Chang Gung University, Kuei-Shan, Taoyuan, Taiwan.
authors: Wen-Ling
authors: WL
authors: Kuo
authors: Ming-Chin
authors: MC
authors: Yu
authors: Ju-Fang
authors: JF
authors: Lee
authors: Chi-Neu
authors: CN
authors: Tsai
authors: Tse-Ching
authors: TC
authors: Chen
authors: Miin-Fu
authors: MF
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000473:pathology; D000068877:Imatinib Mesylate; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D002251:Carbon Tetrachloride