Taipei Medical University

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Wang CH
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------>journal_name=Gene Therapy
------>paper_name=Electroporative alpha-MSH gene transfer attenuates thioacetamide-induced murine hepatic fibrosis by MMP and TIMP modulation
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------>fullAbstract=Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a 13-amino-acid peptide with potent anti-inflammatory effects. We have previously demonstrated that alpha-MSH gene therapy protects against thioacetamide (TAA)-induced acute liver failure. Therefore, the aim of this study is to investigate whether alpha-MSH gene therapy possesses antihepatic fibrogenic effect. Liver fibrosis was induced by long-term TAA administration in mice. alpha-Melanocyte-stimulating hormone expression plasmid was delivered via electroporation after liver fibrosis was established. Our results showed that alpha-MSH gene therapy attenuated liver fibrosis in TAA-treated mice. Reverse transcription polymerase chain reaction revealed that alpha-MSH gene therapy attenuated the liver transforming growth factor-beta1, collagen alpha1 and cell adhesion molecule mRNA upregulation. Following gene transfer, the expression of alpha-smooth muscle actin and cyclooxygenase-2 were both significantly attenuated. Further, alpha-MSH significantly increased matrix metalloproteinase (MMP), while tissue inhibitors of matrix metalloproteinase (TIMPs) were inactivated. In summary, alpha-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, alpha-MSH gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use.
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------>authors2=Lee TH
------>authors3=Chou WY
------>authors4=Hung KS
------>authors5=Concejero AM
------>authors6=Jawan B
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------>authors=Wang CH
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------>updateTitle=Electroporative alpha-MSH gene transfer attenuates thioacetamide-induced murine hepatic fibrosis by MMP and TIMP modulation.
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------>no=13
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------>publish_year=2006
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A B C D E F G H I J K L M N O P Q R S T U V W X Y Z