Alpha-melanocyte-stimulating hormone gene therapy reverses carbon tetrachloride induced liver fibrosis in mice

The Journal of Gene Medicine
Tsung-Hsing LeeCheng-Haung Wang

Abstract

Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. Effective therapies are lacking. We have previously demonstrated that alpha-melanocyte-stimulating hormone (alpha-MSH) gene therapy protects against thioacetamide-induced acute liver failure in mice. Recent reports showed that collagen metabolism is a novel target of alpha-MSH. Therefore, the aim of this study is to investigate whether alpha-MSH gene therapy possesses anti-hepatic fibrogenic effect in mice. Liver fibrosis was induced in mice by administering carbon tetrachloride (CCl4) continuously for 10 weeks. Alpha-MSH expression plasmid was delivered via electroporation after liver fibrosis had been established. Histopathology, reverse-transcription polymerase chain reaction (RT-PCR), immunoblotting, and gelatin zymography were used to investigate its possible mechanisms of action. Alpha-MSH gene therapy reversed established liver fibrosis in CCl4-treated mice. RT-PCR revealed that alpha-MSH gene therapy attenuated the liver TGF-beta1, collagen alpha1, and cell adhesion molecule mRNA upregulation. Following gene transfer, both the activation of alpha-smooth muscle actin (alpha-SMA) and cyclooxygenase-2 (COX-2) was significantl...Continue Reading

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Jan 13, 2021·Pharmaceuticals·Roshan Dinparastisaleh, Mehdi Mirsaeidi

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