Xu Ning, Hurtig Maria, Zhang Xiao-Ying, Ye Qing, Nilsson-Ehle Peter
Department of Clinical Chemistry, Institute of Laboratory Medicine, University Hospital of Lund, Klinikgatan 19, S-221 85 Lund, Sweden.
Biochim Biophys Acta. 2004 Jul 5;1683(1-3):33-7. doi: 10.1016/j.bbalip.2004.04.001.
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-beta), has been shown to decreased apoB secretion in HepG2 cells, and we hypothesized that TGF-beta 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-beta, as well as TGF-alpha, epidermal growth factor (EGF) and hepatic growth factor (HGF). TGF-beta significantly inhibited both apoM and apoB mRNA expression in HepG2 cells. The inhibitory effects of TGF-beta were dose-dependent, i.e. 1 ng/ml of TGF-beta decreased apoM mRNA levels by 30%, and 10 or 100 ng/ml of TGF-beta decreased apoM mRNA levels more than 65%. The effect of TGF-beta on apoB mRNA expression was slightly weaker than that of apoM, with a maximum effect at 10 or 100 ng/ml TGF-beta where apoB mRNA levels decreased about 55%. The inhibitory effects of TGF-beta on apoM and apoB mRNA levels also increased with increasing incubation time, where the maximum effect was obtained at 24 h. Moreover TGF-alpha, EGF and HGF all decreased both apoM and apoB mRNA levels, but to a less extent than TGF-beta. 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.
载脂蛋白M（apoM）是一种新型载脂蛋白，主要存在于人体血浆中的高密度脂蛋白（HDL）中，且仅在肝脏和肾脏中表达。apoM的病理生理功能尚未阐明。载脂蛋白B（apoB）是低密度脂蛋白（LDL）的特征性载脂蛋白，与apoM一样，是一种高度疏水的蛋白质，因此它们都必须在血浆中与脂蛋白颗粒共同循环。细胞因子转化生长因子-β（TGF-β）已被证明可降低HepG2细胞中apoB的分泌，我们推测TGF-β可能对HepG2细胞中apoM的表达有相同作用。在本研究中，我们使用实时逆转录聚合酶链反应（RT-PCR）分析了在给予TGF-β以及转化生长因子-α（TGF-α）、表皮生长因子（EGF）和肝细胞生长因子（HGF）期间apoM和apoB的信使核糖核酸（mRNA）水平。TGF-β显著抑制HepG2细胞中apoM和apoB的mRNA表达。TGF-β的抑制作用呈剂量依赖性，即1纳克/毫升的TGF-β可使apoM的mRNA水平降低30%，而10或100纳克/毫升的TGF-β可使apoM的mRNA水平降低超过65%。TGF-β对apoB的mRNA表达的作用略弱于对apoM的作用，在10或100纳克/毫升的TGF-β时作用最大，此时apoB的mRNA水平降低约55%。TGF-β对apoM和apoB的mRNA水平的抑制作用也随孵育时间的增加而增强，在24小时时达到最大作用。此外，TGF-α、EGF和HGF均降低了apoM和apoB的mRNA水平，但程度低于TGF-β。此外，所有四种细胞因子对apoM的mRNA表达的作用比对apoB的mRNA表达的作用更明显。本研究表明，apoM与apoB一样，可能参与体内肝脏脂蛋白的组装。
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