Tissue-specific function of farnesoid X receptor in liver and intestine.
Tissue-specific function of farnesoid X receptor in liver and intestine.
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DOI：
10.1016/j.phrs.2010.12.018
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发表时间：
2011-04
影响因子：
9.3
通讯作者：
Guo, Grace L.
中科院分区：
文献类型：
--
作者：
Zhu, Yan;Li, Fei;Guo, Grace L.
核受体是一类配体激活的转录因子，参与多种生理、发育和毒理过程。法尼醇X受体（FXR）是属于NR超家族的NR。FXR的内源性配体是胆汁酸。FXR在调节参与维持胆汁酸和脂质稳态的基因网络中是必不可少的。很明显，FXR对肝脏和肠道功能至关重要。在小鼠中，FXR缺乏导致胆汁淤积、胆结石病、非酒精性脂肪性肝炎、肝肿瘤和结肠肿瘤的发展。使用FXR在全身或肝细胞或肠上皮细胞中选择性缺失的小鼠模型，我们开始揭示组织特异性FXR功能在调节胆汁酸和脂质稳态中的重要性。然而，开发组织特异性FXR调节剂以预防和治疗与胆汁酸或脂质紊乱相关的疾病存在巨大挑战。随着对FXR在啮齿动物和人类中功能的进一步了解，这种核受体可能成为预防和治疗肝脏，胃肠道和全身性疾病的新靶点。
Nuclear receptors (NRs) are ligand-activated transcriptional factors that are involved in various physiological, developmental, and toxicological processes. Farnesoid X receptor (FXR) is a NR that belongs to the NR superfamily. The endogenous ligands of FXR are bile acids. FXR is essential in regulating a network of genes involved in maintaining bile acid and lipid homeostasis. It is clear that FXR is critical for liver and intestinal function. In mice FXR deficiency leads to the development of cholestasis, gallstone disease, nonalcoholic steatohepatitis, liver tumor, and colon tumor. Using mouse models where FXR is deleted either in the whole-body, or selectively in hepatocytes or enterocytes, we start to reveal the importance of tissue-specific FXR function in regulating bile acid and lipid homeostasis. However, a great challenge exists for developing tissue-specific FXR modulators to prevent and treat diseases associated with bile acid or lipid disorders. With further understanding of FXR function in both rodents and humans, this nuclear receptor may emerge as a novel target to prevent and treat liver, gastrointestinal and systemic diseases.
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