All-trans retinoic acid diminishes collagen production in a hepatic stellate cell line via suppression of active protein-1 and c-Jun N-terminal kinase signal |
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Authors: | Yuan Ye Zili Dan |
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Institution: | Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China |
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Abstract: | Following acute and chronic liver injury, hepatic stellate cells (HSCs) become activated to undergo a phenotypic transformation
into myofibroblast-like cells and lose their retinol content, but the mechanisms of retinoid loss and its potential roles
in HSCs activation and liver fibrosis are not understood. The influence of retinoids on HSCs and hepatic fibrosis remains
controversial. The purpose of this study was to evaluate the effects of all-trans retinoid acid (ATRA) on cell proliferation,
mRNA expression of collagen genes procollagen α1 (I), procollagen α1 (III)], profibrogenic genes (TGF-β1, CTGF, MMP-2, TIMP-1, TIMP-2, PAI-1), fibrolytic genes (MMP-3, MMP-13) and the upstream element (JNK and AP-1) in the rat
hepatic stellate cell line (CFSC-2G). Cell proliferation was evaluated by measuring BrdU incorporation. The mRNA expression
levels of collagen genes procollagen α1 (I), procollagen α1 (III)], profibrogenic genes (TGF-β1, CTGF, MMP-2, TIMP-1, TIMP-2, PAI-1), and fibrolytic genes (MMP-3, MMP-13) were quantitatively detected by using real-time
PCR. The mRNA expression of JNK and AP-1 was quantified by RT-PCR. The results showed that ATRA inhibited HSCs proliferation
and diminished the mRNA expression of collagen genes procollagen α1 (I), procollagen α1 (III)] and profibrogenic genes (TGF-β1, CTGF, MMP-2, TIMP-1, TIMP-2, PAI-1), and significantly stimulated the mRNA expression of MMP-3 and MMP-13 in HSCs by suppressing
the mRNA expression of JNK and AP-1. These findings suggested that ATRA could inhibit proliferation and collagen production
of HSCs via the suppression of active protein-1 and c-Jun N-terminal kinase signal, then decrease the mRNAs expression of
profibrogenic genes (TGF-β1, CTGF, MMP-2, TIMP-1, TIMP-2, PAI-1), and significantly induce the mRNA expression of MMP-3 and MMP-13. |
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Keywords: | all trans-retinoic acid liver stellate cells collagen transforming growth factor β1 activeprotein-1 c-Jun N-terminal kinase |
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