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PI-3 K/AKT and ERK signaling pathways mediate leptin-induced inhibition of PPARγ gene expression in primary rat hepatic stellate cells

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Abstract

Compelling evidence indicates the pro-fibrogenic action of leptin in liver. Peroxisome proliferator-activated receptor-γ (PPARγ) can reverse hepatic stellate cell (HSC) activation and maintain HSC quiescence. HSC activation, a key step in the development of liver fibrosis, is coupled with the up-expression of leptin and the dramatic down-expression of PPARγ. The present study is aimed to assess the effect of leptin on PPARγ gene expression in primary cultured rat HSCs and investigate the related mechanisms by using Western blotting analysis, real-time PCR, transient transfection approach, and cell growth analysis. The results suggest that leptin negatively regulates PPARγ gene expression at mRNA level, protein level and PPARγ gene promoter activity level in HSCs. The inhibitory effect of leptin on PPARγ gene expression contributes to cell growth of activated HSCs in vitro. Phosphatidylinositol 3-kinase/AKT (PI-3 K/AKT) and extracellular signal-regulated kinase (ERK) signaling pathways mediate the leptin-induced inhibition of PPARγ gene expression. In summary, these findings suggest that leptin down-regulates PPARγ gene expression through activation of PI-3 K/AKT or ERK signaling pathway in primary cultured rat HSCs. Our results might provide novel insights into the mechanisms for the pro-fibrogenic action of leptin in liver.

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Acknowledgments

This study was supported by a grant from the Natural Science Fund for College and University in Jiangsu Province (Grant Number: 07KJB310094) and a grant from Postdoctor Fund of Nantong University.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Medical College, Nantong University, Nantong, 226001, Jiangsu, China

    Yajun Zhou, Xin Jia & Xin Wang

  2. Institute of Nautical Medicine, Nantong University, Nantong, China

    Guohua Wang

  3. Jiangsu Province Key Lab of Neuroregeneration, Nantong University, Nantong, China

    Jie Liu

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  1. Yajun Zhou
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  2. Xin Jia
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  4. Xin Wang
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Correspondence to Yajun Zhou.

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Zhou, Y., Jia, X., Wang, G. et al. PI-3 K/AKT and ERK signaling pathways mediate leptin-induced inhibition of PPARγ gene expression in primary rat hepatic stellate cells. Mol Cell Biochem 325, 131–139 (2009). https://doi.org/10.1007/s11010-009-0027-3

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  • DOI: https://doi.org/10.1007/s11010-009-0027-3

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