Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration
Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration
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DOI：
10.1126/science.1121435
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发表时间：
2006-04-14
期刊：
影响因子：
56.9
通讯作者：
Moore, DD
中科院分区：
文献类型：
--
作者：
Huang, WD;Ma, K;Moore, DD
肝脏质量依赖于一个或多个不明体液信号，当肝脏功能能力减弱时，这些体液信号会推动再生。胆汁酸是重要的肝脏产品，其水平受到严格控制。在这里，我们确定了核受体依赖的胆汁酸信号在正常肝再生中的作用。胆汁酸水平的升高会加速再生，而胆汁酸水平的降低会抑制肝脏的再生，而初级核胆汁酸受体FXR的缺失也是如此。我们认为，胆汁酸流量增加引起的FXR激活是肝脏功能减退的信号。FXR，可能还有其他核受体，可能不仅通过调节适当的代谢靶基因的表达，而且通过促进同源营养性肝脏生长来促进体内平衡。
Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor - dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.