FGF21 inhibits apolipoprotein(a) expression in HepG2 cells via the FGFR1-ERK1/2-Elk-1 pathway.
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.
Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, China, 493814078@qq.com.
Xiaolong
X
Lin
Guohua
G
Li
Xinglan
X
He
Xiaofeng
X
Ma
Kai
K
Zhang
Hai
H
Zhang
Gaofeng
G
Zeng
Zuo
Z
Wang
D017667:Adipocytes; D053241:Apoprotein(a) / Q000096:biosynthesis* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D050807:ets-Domain Protein Elk-1 / Q000235:genetics* / Q000378:metabolism
D050807:ets-Domain Protein Elk-1; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D053241:Apoprotein(a)