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J Gastrointest Surg. 2012 Feb;16(2):361-9. doi: 10.1007/s11605-011-1764-7. Epub 2011 Nov 9.

Imatinib mesylate improves liver regeneration and attenuates liver fibrogenesis in CCL4-treated mice.

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1
Department of Surgery, Chang Gung Memorial Hospital and Medical School of Chang Gung University, Kuei-Shan, Taoyuan, Taiwan.

Abstract

BACKGROUNDS:

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.

AIMS:

This study aimed to further evaluate the role of STI-571 in liver regeneration.

MATERIALS AND METHODS:

All animals were divided into four groups, and mice were treated with or without CCL(4) and STI-571 (nā€‰=ā€‰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 (pā€‰<ā€‰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.

CONCLUSION:

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.

PMID:
22068968
DOI:
10.1007/s11605-011-1764-7
[Indexed for MEDLINE]
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