High density lipoprotein receptor gene, its structure and expression.

高密度脂蛋白(高密度脂蛋白)是一种抗动脉粥样硬化的脂蛋白，由几个组成和代谢功能不同的亚类组成。这种生理上的复杂性似乎与越来越多的候选高密度脂蛋白受体相匹配，因为最近在各种组织中发现了几种高密度脂蛋白结合蛋白。确定它们的结构和在高密度脂蛋白代谢中的潜在作用是很重要的。我们克隆了一个候选的高密度脂蛋白受体HB2，它是首先从大鼠肝脏中纯化的一对高密度脂蛋白结合蛋白(HB1和HB2)之一。为了阐明HB2的调控和功能，我们研究了已知影响基因表达的细胞因子、胆汁酸和脂溶维生素对HB2表达的影响。Hb_2存在于单核细胞THP-1细胞中，在佛波酯(PMA)分化的巨噬细胞中显著上调，并且对这些细胞的胆固醇负荷很敏感。尽管胰岛素和IGF-1对HB2的表达没有影响，但某些细胞因子，如TNF-α、IL-6和M-CSF，可显著降低THP-1细胞中HB2的表达。已知胆汁酸可上调胆固醇代谢相关基因的表达。牛磺胆酸和鹅去氧胆酸也显著增加Hb2的表达，视黄醇和1，25-维生素D3不改变Hb2的表达，而25-VD3则增加Hb2mRNA的表达。α-生育酚显著降低PMA分化的THP-1巨噬细胞Hb2mRNA表达。为了阐明L-IMG-CoA还原酶抑制剂是否影响Hb2mRNA表达水平，我们观察了辛伐他汀对兔Hb2mRNA表达的影响。辛伐他汀治疗3周后，大鼠肝、肺组织胆固醇含量明显降低。辛伐他汀治疗可显着降低兔肝、肺中HB2的mRNA水平，抑制HB2也可能具有抗动脉粥样硬化的作用；因此，这是HMG-CoA还原酶抑制剂的另一个特点。

High density lipoprotein (HDL), an antiatherogenic lipoprotein comprises several subclasses differing in composition and metabolic function. This physiological complexity appears to be matched with the growing number of candidate HDL receptors, since several HDL binding proteins have recently been identified in various tissues. It is important to identify their structure and potential role in HDL metabolism. We have cloned a candidate HDL receptor, HB2, which is one of a pair of HDL binding proteins (HBl and HB2) first purified from rat liver. To elucidate the regulation and function of HB2, we studied the effect of cytokines, bile acids and fat-soluble vitamins, which are known to affect gene expression, on the HB2 expression. HB_2, minimally present in monocytic THP-1 cells, is substantially upregulated in phorbol ester (PMA)-differentiated macrophages and appears sensitive to cholesterol loading of these cells. Although Insulin and IGF-1 did not influence HB2 expression, some cytokines, TNF-alpha, IL-6 and M-CSF, strongly reduced expression of HB2 in THP-1 cells. It is known that bile acids up-regulate expression of genes related to cholesterol metabolism. Taurocholate and chenodeoxycholate also increased HB2 expression significantly.- Retinol and 1,25-vitamin D_3 did not change HB2 expression, however, 25-vitamin D_3 increased HB2 mRNA in THP-1 cells. alpha-Tocopherol significantly reduced HB2 mRNA expression in PMA-differentiated THP- 1 macrophages.To elucidate whether an l-IMG-CoA reductase inhibitor affects mRNA levels of HB2 expression, we investigated the effect of simvastatin in rabbits. After three weeks administration of simvastatin, cholesterol contents in liver and lung were decreased. Simvastatin treatment significantly reduced the levels of HB2 mRNA in the liver and lung of rabbits Suppression of HB2 may also be antiatherogenic ; therefore it is an another feature of HMG-CoA reductase inhibitors.