肝细胞特异性突变确立视黄酸X受体α作为肝脏中多种生理过程的异二聚体整合因子。
Hepatocyte-specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver.
作者信息
Wan Y J, An D, Cai Y, Repa J J, Hung-Po Chen T, Flores M, Postic C, Magnuson M A, Chen J, Chien K R, French S, Mangelsdorf D J, Sucov H M
机构信息
Department of Pathology, Harbor-UCLA Medical Center, Torrance, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
出版信息
Mol Cell Biol. 2000 Jun;20(12):4436-44. doi: 10.1128/MCB.20.12.4436-4444.2000.
A large number of physiological processes in the adult liver are regulated by nuclear receptors that require heterodimerization with retinoid X receptors (RXRs). In this study, we have used cre-mediated recombination to disrupt the mouse RXRalpha gene specifically in hepatocytes. Although such mice are viable, molecular and biochemical parameters indicate that every one of the examined metabolic pathways in the liver (mediated by RXR heterodimerization with PPARalpha, CARbeta, PXR, LXR, and FXR) is compromised in the absence of RXRalpha. These data demonstrate the presence of a complex circuitry in which RXRalpha is integrated into a number of diverse physiological pathways as a common regulatory component of cholesterol, fatty acid, bile acid, steroid, and xenobiotic metabolism and homeostasis.
成年肝脏中的大量生理过程受核受体调控，这些核受体需要与视黄酸X受体（RXRs）形成异源二聚体。在本研究中，我们利用cre介导的重组技术，特异性地在肝细胞中破坏小鼠RXRα基因。尽管此类小鼠能够存活，但分子和生化参数表明，在缺乏RXRα的情况下，肝脏中每条被检测的代谢途径（由RXR与PPARα、CARβ、PXR、LXR和FXR形成异源二聚体介导）均受到损害。这些数据表明存在一个复杂的调控网络，其中RXRα作为胆固醇、脂肪酸、胆汁酸、类固醇和外源性物质代谢及稳态的共同调节成分，被整合到多种不同的生理途径中。
Zotero 插件