Bridging cell surface receptor with nuclear receptors in control of bile acid homeostasis.
Bridging cell surface receptor with nuclear receptors in control of bile acid homeostasis.
复制标题
将细胞表面受体与核受体桥接以控制胆汁酸稳态。
DOI：
10.1038/aps.2014.118
复制
发表时间：
2015
影响因子：
8.2
通讯作者：
Feng,Gen-sheng
中科院分区：
文献类型：
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作者：
Li,Shuangwei;Ni,Andrew;Feng,Gen-sheng
胆汁酸（BAs）由于其两亲性，传统上被认为是乳化疏水性脂类和维生素的“生理洗涤剂”。但越来越多的临床和实验证据表明，BA体内平衡被破坏与各种肝脏疾病（包括肝炎感染、糖尿病和癌症）之间存在关联。因此，BA稳态调节已成为一个备受关注和研究的领域。在确定Farnesoid X受体（FXR）是BAs的内源性受体后，几个核受体（SHP， HNF4α和LRH-1）也被发现在BA稳态调节中起重要作用。这些核受体的一些翻译后修饰已经被证实，但它们的生理意义仍然是难以捉摸的。肠道分泌FGF15/19，可激活肝脏FGFR4及其下游信号级联，导致肝脏BA生物合成受到抑制。然而，活化激酶和这些核受体之间的联系尚未完全阐明。在此，我们回顾了最近关于BA稳态信号串扰的文献。
Bile acids (BAs) are traditionally considered as “physiological detergents” for emulsifying hydrophobic lipids and vitamins due to their amphipathic nature. But accumulating clinical and experimental evidence shows an association between disrupted BA homeostasis and various liver disease conditions including hepatitis infection, diabetes and cancer. Consequently, BA homeostasis regulation has become a field of heavy interest and investigation. After identification of the Farnesoid X Receptor (FXR) as an endogenous receptor for BAs, several nuclear receptors (SHP, HNF4α, and LRH-1) were also found to be important in regulation of BA homeostasis. Some post-translational modifications of these nuclear receptors have been demonstrated, but their physiological significance is still elusive. Gut secrets FGF15/19 that can activate hepatic FGFR4 and its downstream signaling cascade, leading to repressed hepatic BA biosynthesis. However, the link between the activated kinases and these nuclear receptors is not fully elucidated. Here, we review the recent literature on signal crosstalk in BA homeostasis.