FXR-SHP通路是肝脏调节胆汁代谢的关键通路。 FXR通过结合SHP基因启动子区域的FXR结合位点 (FXR Response Element, FXRRE),又称IR1序列,以调控SHP基因的转录表达，进而维持肝脏胆汁合成与代谢稳态。 作为FXR最主要的下游基因，SHP与肝脏肿瘤形成关系密切。

Our findings demonstrate a role for the FXR-SHP axis in maintaining glycoprotein diversity in the liver. N-Glycosylation is a key posttranslational modification that decides the fate of several liver proteins, including their targeting to the plasma membrane or for secretion.

Farnesoid X receptor/retinoid X receptor-alpha (FXR/RXRα) is the master transcriptional regulator of bile salt synthesis and transport in liver and intestine. FXR is activated by bile acids, RXRα by the vitamin A–derivative 9-cis retinoic acid (9cRA).

Sep 30, 2008 · FXR activates the expression of short heterodimer partner (SHP), which in turn binds to and inactivates liver receptor homolog 1 (LRH-1, NR5A2), thus potently inhibiting the expression of ...

May 15, 2004 · SHP is an FXR target gene that represses the activity of several nuclear receptors, including LRH-1 and LXR, which are essential for the transcription of cholesterol 7α-hydroxylase (CYP7A1; see Table 1), the rate-limiting enzyme in bile acid biosynthesis.

Combined deletion of the hepatic FXR/SHP axis improves glucose/fatty acid homeostasis in aged mice, reversing the aging phenotype of body weight gain, increased adiposity, and glucose/insulin tolerance, suggesting a central role of this axis in whole-body energy homeostasis.

Sep 1, 2000 · Through the use of a potent, nonsteroidal FXR ligand, we have identified SHP-1 as an FXR target gene in the liver of humans and rodents. Furthermore, we have demonstrated that SHP-1 can interact with LRH-1 and efficiently repress expression of CYP7A1.

We have used a potent, nonsteroidal FXR ligand to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain.

Apr 21, 2021 · Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation.

Feb 3, 2014 · FXR/CDCA-activated expression of SHP is primarily mediated through direct binding to an LRH-1 binding site, which is not modulated by LRH-1 and unresponsive to 9cRA. 9cRA-induced expression of SHP requires the IR-1 that overlaps with a …