High density lipoprotein receptor gene, its structure and expression.

高密度脂蛋白（HDL）是一种抗动脉粥样硬化的脂蛋白，包括几个在组成和代谢功能上不同的亚类。这种生理复杂性似乎与越来越多的候选HDL受体相匹配，因为最近在各种组织中鉴定出了几种HDL结合蛋白。重要的是要确定它们的结构和在HDL代谢中的潜在作用。我们已经克隆了一个候选HDL受体，HB 2，它是一对HDL结合蛋白（HB 1和HB 2）首先从大鼠肝脏中纯化。为了阐明HB 2的调节和功能，我们研究了已知影响基因表达的细胞因子、胆汁酸和脂溶性维生素对HB 2表达的影响。HB_2在单核细胞THP-1细胞中最少，在佛波酯（PMA）分化的巨噬细胞中显著上调，并且似乎对这些细胞的胆固醇负荷敏感。虽然胰岛素和IGF-1不影响HB 2的表达，但一些细胞因子TNF-α、IL-6和M-CSF强烈降低THP-1细胞中HB 2的表达。已知胆汁酸上调与胆固醇代谢相关的基因的表达。牛磺胆酸盐和鹅脱氧胆酸盐也显著增加HB 2表达。视黄醇和1，25-维生素D_3对THP-1细胞中HB 2的表达无明显影响，而25-维生素D_3可使HB 2 mRNA的表达增加。为了阐明l-IMG-CoA还原酶抑制剂是否影响HB 2表达的mRNA水平，我们研究了辛伐他汀在兔中的作用。辛伐他汀治疗3周后，肝、肺组织胆固醇含量明显降低。辛伐他汀治疗显著降低了兔肝和肺中HB 2 mRNA的水平。抑制HB 2也可能是抗动脉粥样硬化的;因此，它是HMG-CoA还原酶抑制剂的另一个特征。

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.