Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Cardiovascular Metabolic Renal (CMR)-Research Center, 10115 Berlin, Germany.
Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, A-8010 Graz, Austria.
Nutrients. 2022 Mar 15;14(6):1236. doi: 10.3390/nu14061236.
Retinol binding protein 4 (RBP4) is the specific transport protein of the lipophilic vitamin A, retinol, in blood. Circulating RBP4 originates from the liver. It is secreted by hepatocytes after it has been loaded with retinol and binding to transthyretin (TTR). TTR association prevents renal filtration due to the formation of a higher molecular weight complex. In the circulation, RBP4 binds to specific membrane receptors, thereby delivering retinol to target cells, rendering liver-secreted RBP4 the major mechanism to distribute hepatic vitamin A stores to extrahepatic tissues. In particular, binding of RBP4 to 'stimulated by retinoic acid 6' (STRA6) is required to balance tissue retinoid responses in a highly homeostatic manner. Consequently, defects/mutations in RBP4 can cause a variety of conditions and diseases due to dysregulated retinoid homeostasis and cover embryonic development, vision, metabolism, and cardiovascular diseases. Aside from the effects related to retinol transport, non-canonical functions of RBP4 have also been reported. In this review, we summarize the current knowledge on the regulation and function of RBP4 in health and disease derived from murine models and human mutations.
视黄醇结合蛋白 4（RBP4）是血液中亲脂性维生素 A、视黄醇的特异性转运蛋白。循环中的 RBP4 来源于肝脏。它在与转甲状腺素蛋白（TTR）结合后被肝细胞装载视黄醇并分泌。TTR 结合物的形成阻止了肾脏的过滤，因为它形成了更高分子量的复合物。在循环中，RBP4 与特定的膜受体结合，从而将视黄醇递送至靶细胞，使肝脏分泌的 RBP4 成为将肝脏维生素 A 储存分配到肝外组织的主要机制。特别是，RBP4 与“视黄酸受体应答基因 6（STRA6）”的结合对于以高度动态平衡的方式平衡组织视黄醛反应是必需的。因此，由于视黄醛稳态失调，RBP4 的缺陷/突变可导致各种病症，涵盖胚胎发育、视力、代谢和心血管疾病。除了与视黄醇转运相关的作用外，还报道了 RBP4 的非典型功能。在这篇综述中，我们总结了源自鼠模型和人类突变的 RBP4 在健康和疾病中的调节和功能的现有知识。
