Electroporative α-MSH gene transfer attenuates thioacetamide-induced murine hepatic fibrosis by MMP and TIMP modulation

C. H. Wang, T. H. Lee, C. N. Lu, W. Y. Chou, K. S. Hung, A. M. Concejero, B. Jawan

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20 引文 斯高帕斯(Scopus)


Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino-acid peptide with potent anti-inflammatory effects. We have previously demonstrated that α-MSH gene therapy protects against thioacetamide (TAA)-induced acute liver failure. Therefore, the aim of this study is to investigate whether α-MSH gene therapy possesses antihepatic fibrogenic effect. Liver fibrosis was induced by long-term TAA administration in mice. α-Melanocyte-stimulating hormone expression plasmid was delivered via electroporation after liver fibrosis was established. Our results showed that α-MSH gene therapy attenuated liver fibrosis in TAA-treated mice. Reverse transcription polymerase chain reaction revealed that α-MSH gene therapy attenuated the liver transforming growth factor-β1, collagen α1 and cell adhesion molecule mRNA upregulation. Following gene transfer, the expression of α-smooth muscle actin and cyclooxygenase-2 were both significantly attenuated. Further, α-MSH significantly increased matrix metalloproteinase (MMP), while tissue inhibitors of matrix metalloproteinase (TIMPs) were inactivated. In summary, α-MSH gene therapy reversed established liver fibrosis in mice and prevented the upregulated fibrogenic and pro-inflammatory gene responses after TAA administration. Its collagenolytic effect might be attributed to MMP and TIMP modulation. Hence, α-MSH gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use.
頁(從 - 到)1000-1009
期刊Gene Therapy
出版狀態已發佈 - 7月 2006

ASJC Scopus subject areas

  • 分子醫學
  • 分子生物學
  • 遺傳學


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