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FGF21 inhibits apolipoprotein(a) expression in HepG2 cells via the FGFR1-ERK1/2-Elk-1 pathway

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Abstract

Lipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein, whose metabolism is poorly understood. Efficient and secure drugs that can lower elevated plasma Lp(a) concentrations are currently lacking. Fibroblast growth factor-21 (FGF-21), a member of the FGFS super family, regulates glucose and lipid metabolism in hepatocytes and adipocytes via FGFR-ERK1/2 signaling. In this study, we investigated the molecular mechanisms that influence apolipoprotein(a) [apo(a)] biosynthesis. We also determined the effects of FGF21 on HepG2 cell apo(a) expression and secretion, as well as the mechanism of FGF21 in these effects. Results showed that FGF21 inhibited apo(a) expression at both mRNA and protein levels in a dose- and time--dependent manner and then suppressed the secretion of apo(a). These effects were attenuated by PD98059 (ERK1/2 inhibitor) and Elk-1 siRNA. PD166866 (FGFR1 inhibitor) also attenuated the FGF21-mediated inhibition of apo(a) expression and inhibited ERK1/2 and Elk-1 activation. These results demonstrate that FGF21 suppresses apo(a) expression via the FGFR1-ERK1/2-Elk-1 pathway.

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Acknowledgments

This study was supported by the Innovative Research Team for Science and Technology in Higher Educational Institutions of Hunan Province and Natural Science Foundation of China (No. 81070221) and Visiting Scholar Foundation of Key Laboratory for Biorheological Science, and Technology (Chongqing University) of Ministry of Education (2010).

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Authors and Affiliations

  1. Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, China

    Xiaolong Lin, Guohua Li, Xinglan He, Xiaofeng Ma, Kai Zhang & Zuo Wang

  2. The Second Affiliated Hospital of the University of South China, Hengyang, 421001, China

    Hai Zhang & Gaofeng Zeng

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  1. Xiaolong Lin
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  2. Guohua Li
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  3. Xinglan He
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  4. Xiaofeng Ma
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  5. Kai Zhang
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  6. Hai Zhang
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  7. Gaofeng Zeng
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  8. Zuo Wang
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Corresponding author

Correspondence to Zuo Wang.

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Guohua Li: co-first author.

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Lin, X., Li, G., He, X. et al. FGF21 inhibits apolipoprotein(a) expression in HepG2 cells via the FGFR1-ERK1/2-Elk-1 pathway. Mol Cell Biochem 393, 33–42 (2014). https://doi.org/10.1007/s11010-014-2044-0

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  • DOI: https://doi.org/10.1007/s11010-014-2044-0

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