Transforming growth factor-beta down-regulates apolipoprotein M in HepG2 cells

Abstract

Apolipoprotein M (apoM) is a novel apolipoprotein presented mostly in high-density lipoprotein (HDL) in human plasma, and is exclusively expressed in liver and in kidney. The pathophysiological function of apoM has not yet been elucidated. Apolipoprotein B (apoB), the characteristic apolipoprotein of low-density lipoprotein (LDL), is like apoM, a very hydrophobic protein, and thereafter they both must co-circulate with lipoprotein particles in plasma. The cytokine, transforming growth factor-beta (TGF-β), has been shown to decreased apoB secretion in HepG2 cells, and we hypothesized that TGF-β may have the same effects on apoM expression in HepG2 cells. In the present study, we used real-time RT-PCR to analyze apoM and apoB mRNA levels during administration of TGF-β, as well as TGF-α, epidermal growth factor (EGF) and hepatic growth factor (HGF). TGF-β significantly inhibited both apoM and apoB mRNA expression in HepG2 cells. The inhibitory effects of TGF-β were dose-dependent, i.e. 1 ng/ml of TGF-β decreased apoM mRNA levels by 30%, and 10 or 100 ng/ml of TGF-β decreased apoM mRNA levels more than 65%. The effect of TGF-β on apoB mRNA expression was slightly weaker than that of apoM, with a maximum effect at 10 or 100 ng/ml TGF-β where apoB mRNA levels decreased about 55%. The inhibitory effects of TGF-β on apoM and apoB mRNA levels also increased with increasing incubation time, where the maximum effect was obtained at 24 h. Moreover TGF-α, EGF and HGF all decreased both apoM and apoB mRNA levels, but to a less extent than TGF-β. Further, all four cytokines had more pronounced effects on apoM mRNA expression than apoB mRNA expression. The present study suggested that apoM, like apoB, may be involved in the hepatic lipoprotein assembly in vivo.