Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Einsteinweg 55, PO Box 9502, 2300RA Leiden, The Netherlands.
World J Gastroenterol. 2010 Dec 21;16(47):5916-24. doi: 10.3748/wjg.v16.i47.5916.
Scavenger receptor class B type I (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identifies SR-BI as a multi-purpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is efficiently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insufficiency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoB-containing lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI deficiency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insufficiency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has significantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identified SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function.
清道夫受体 B 类 I 型（SR-BI）是清道夫受体家族中的一种重要的整合膜糖蛋白。本综述重点介绍了 SR-BI 基因敲除小鼠的研究，这些研究涉及 SR-BI 在胆固醇和类固醇代谢中的作用。肝细胞中的 SR-BI 是唯一参与从高密度脂蛋白（HDL）中选择性摄取胆固醇酯的分子。SR-BI 在结合和摄取含有天然载脂蛋白 B（apoB）的脂蛋白方面具有生理作用，这表明 SR-BI 是从血液循环中摄取脂蛋白进入肝细胞的多功能参与者。在肾上腺皮质细胞中，SR-BI 介导 HDL 胆固醇酯的选择性摄取，这与糖皮质激素（即皮质酮）的合成有效偶联。SR-BI 基因敲除小鼠患有肾上腺糖皮质激素不足，这表明功能性 SR-BI 蛋白是小鼠最佳肾上腺类固醇生成所必需的。巨噬细胞中的 SR-BI 在胆固醇代谢中发挥双重作用，因为它能够摄取与 HDL 和含有 apoB 的脂蛋白相关的胆固醇，并可能有助于胆固醇向 HDL 的流出。SR-BI 的缺失与血小板减少和血栓形成易感性改变有关，这表明 SR-BI 在调节小鼠血小板数量和功能方面具有新的作用。在人源化 SR-BI 基因敲除小鼠中转基因表达胆固醇酯转移蛋白可使 HDL 胆固醇酯的肝脏摄取正常化。然而，与 SR-BI 缺乏相关的其他病理，即增加动脉粥样硬化易感性、肾上腺糖皮质激素不足和血小板功能受损，并未正常化，这表明 SR-BI 在人类胆固醇和类固醇代谢中具有重要作用。总之，SR-BI 基因敲除小鼠的产生极大地促进了我们对 SR-BI 生理作用的认识。使用这些小鼠的研究表明，SR-BI 是胆固醇和类固醇代谢中的多功能参与者，因为它在胆固醇逆向转运、肾上腺类固醇生成和血小板功能中具有不同的作用。
