Nuclear receptor FXR, bile acids and liver damage: Introducing the progressive familial intrahepatic cholestasis with FXR mutations
Nuclear receptor FXR, bile acids and liver damage: Introducing the progressive familial intrahepatic cholestasis with FXR mutations
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DOI：
10.1016/j.bbadis.2017.09.019
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发表时间：
2018-04-01
影响因子：
6.2
通讯作者：
Moschetta, Antonio
中科院分区：
文献类型：
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作者：
Cariello, Marica;Piccinin, Elena;Moschetta, Antonio
核受体法尼醇 X 受体 (FXR) 是胆汁酸 (BA) 稳态的主要调节因子，因为它通过转录驱动沿肠肝轴的 BA 合成、流入、流出和解毒的调节。由于其至关重要的作用，FXR 的改变参与了肝脏和肠道中大量与 BA 相关的炎症性疾病的进展。迄今为止，FXR 通路参与胆汁淤积的发展和治疗已被阐明，FXR 激活疗法在这种情况下具有直接作用。然而，最近发现的一种与 FXR 突变相关的新型遗传性进行性家族性肝内胆汁淤积症 (PFIC) 也增强了绕过 FXR 激活的靶向治疗的真正有益效果，直接促进其靶标（即肠因子 FGF19）在抑制肝 BA 合成中的作用，同时降低肝脏和血清中的总 BA 水平，从而实现了以下目标之一： 胆汁淤积的主要目标。本文是题为“健康与疾病中的胆管细胞”的特刊的一部分，由 Jesus Banales、Marco Marzioni 和 Peter Jansen 编辑。
The nuclear receptor farnesoid X receptor (FXR) is the master regulator of bile acids (BAs) homeostasis since it transcriptionally drives modulation of BA synthesis, influx, efflux, and detoxification along the enterohepatic axis. Due to its crucial role, FXR alterations are involved in the progression of a plethora of BAs associated inflammatory disorders in the liver and in the gut. The involvement of the FXR pathway in cholestasis development and management has been elucidated so far with a direct role of FXR activating therapy in this condition. However, the recent identification of a new type of genetic progressive familial intrahepatic cholestasis (PFIC) linked to FXR mutations has strengthen also the bona fide beneficial effects of target therapies that bypass FXR activation, directly promoting the action of its target, namely the enterokine FGF19, in the repression of hepatic BAs synthesis with reduction of total BA levels in the liver and serum, accomplishing one of the major goals in cholestasis. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.