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Decreased expression of FXR is associated with obstructive cholestasis.
We combined hydrogen deuterium exchange mass spectrometry with computational studies for dissecting molecular recognition and conformational impact of prenylflavonoid interactions on the ligand binding domain of FXR.
Study shows that FXR is phosphorylated at Y67 by non-receptor tyrosine kinase, Src, in response to postprandial FGF19 which is critical for its nuclear localization and transcriptional regulation of bile acids levels and identifies Src-mediated FXR phosphorylation as a potential therapeutic target and biomarker for bile acids-related enterohepatic diseases.
FXR protein levels vary markedly between normal liver, NAFLD without NASH, and NASH. Low levels of FXR are independently associated with NASH.
FXR pathway activation increases XBP1 splicing and enhances p-IRE1alpha expression in liver
Activation of FXR inhibits, whereas TGR5 activation may promote, cholangiocarcinoma progression by regulating proliferation, migration and mitochondrial energy metabolism.
study demonstrated for the first time a novel target for farnesoid X-activated receptor (FXR) and that the activated receptor alters the acquisition of sperm fertilising ability
Low FXR expression is associated with colorectal cancer.
Studies indicate that the deregulation of farnesoid X receptor (FXR) may lead to abnormalities of specific organs and metabolic dysfunction [Review].
FXR agonist treatment enhanced TGF-beta-induced epithelial mesenchymal transition(EMT) morphologic changes and FXR antagonist inhibited the effect of TGF-beta;. Thus, FXR activation enhances EMT in hepatocellular carcinoma (HCC) and FXR antagonists may be EMT-suppressing drug candidates.
This study provides some data suggesting the possible involvement of FXR in the pathophysiology and development of thyroid neoplasms. In particular, we found that there are differences regarding FXR expression between papillary carcinomas and hyperplastic nodules, being also correlated with some patients' clinicopathological parameters.
Data suggest that TGR5 and FXR in intestinal mucosa are important for glucose homeostasis, in particular in metabolic disorders such as type 2 diabetes and obesity. (TGR5 = membrane-type receptor for bile acids TGR5; FXR = farnesoid X receptor) [REVIEW; Congress as Topic]
These results suggested that FXR may serve as an important negative regulator for manipulating Smad3 expression, and the FXR/Smad3 pathway may be a novel target for the treatment of renal fibros
Loss of FXR or its down-regulation is associated with higher bile acids concentrations and with a pro-tumorigenic phenotype. (Review)
Lys-325 is a non-canonical site of SUMOylation of human FXR.CK2 is the priming effector that phosphorylates Ser-327, resulting in enhanced SUMO2 conjugation, which then directs the ubiquitination and degradation of FXR through the recruitment of the SUMO-dependent ubiquitin E3 ligase RNF4.
we proposed a model to link FXR to Sp1, which included triggered FXR, p38/MAPK and/or PI3K/AKT signaling and phosphorylated Sp1, to illustrate the potential crosstalk between the two factors.
the presented evidence suggested that WA can inhibit HCC cell proliferationand tumorigenesis through miR-22-repressed CCNA2, which was at least partially through FXR regulation
The results indicated that epigenetically regulated miR-449a targets CREB5 to increase FXRalpha expression, thereby promoting HBV replication and gene expression. Our findings provide a new understanding of the role of miRNAs in HBV replication
In diabetic humans, there is decreased FXR expression in the kidney. FXR plays an important role in Diabetic Kidney Disease.
FXR regulates serum triglyceride level in part through PLA2G12B.
results suggest that hypothyroidism induces a moderate non-alcoholic steatohepatitis, alllowing the hepatic regeneration. The FXRalpha may be involved in the development of non-alcoholic steatohepatitis in hypothyroid subjects.
FXR is expressed in the ovary, in all regions of the oviduct, and all portions of the vagina of rabbits.
The induction of P450 epoxygenase expression and epoxyeicosatrienoic acids levels is a novel feature of FXR activation in nonalcoholic fatty liver disease.
FXR represents an intrinsic apoptosis inhibitor in hepatocytes and can be targeted via restoring its expression or strengthening FXR/CASP8 interaction for inhibiting hepatocytes apoptosis in liver fibrosis.
Study shows that FXR is phosphorylated at Y67 by non-receptor tyrosine kinase, Src, in response to postprandial Fgf15 which is critical for its nuclear localization and transcriptional regulation of bile acids (BA) levels. Liver-specific expression of phospho-defective Y67F-FXR in mice results in impaired responses to acute BA feeding and exacerbates cholestatic pathologies upon drug-induced hepatobiliary insults.
Study provides a novel finding that suppression of miR-194 attenuates dietary-induced NAFLD via upregulation of FXR/Nr1h4.
FXR-dependent concomitant relationships between gut microbiota, bile acids, and metabolic diseases in both genders.
The role of the CAR signaling pathways within testis was validated using specific CAR agonist (TCPOBOP) and inverse agonist (androstanol) that respectively inhibited or reproduced the phenotype observed in Fxralpha-/- males fed Bile acids (BAs)-diet. These data open interesting perspectives to better define how BA homeostasis contributes to physiological or pathophysiological conditions via the modulation of CAR activity.
Study identified an FXR/beta-catenin interaction whose modulation through beta-catenin suppression promotes FXR activation and decreases hepatic bile acids, which may provide unique therapeutic opportunities in cholestatic liver diseases
Farnesoid X receptor gene deficiency impairs urine concentration in renal medulla.
Data, including data from studies using knockout mice, suggest that control of whole-body energy expenditure by Gcgr agonism requires intact Fxr signaling and Fgf21 secretion in liver. (Gcgr = glucagon receptor glucagon; Fxr = farnesoid X receptor; Fgf21 = fibroblast growth factor-21)
FXR exerts its function in L cells through interacting with CREB, a crucial transcriptional regulator of cAMP-CREB signaling pathway, to inhibit its transcriptional activity. Targeting FXR to rescue GLP-1 secretion may be a promising strategy for type II diabetes.
The underlying mechanism of curcumin against cholestasis was restoring bile acid homeostasis and antagonizing inflammatory responses in a FXR-dependent manner and in turn contributed to overall cholestasis attenuation.
FXR alpha helps establish and maintain an undifferentiated germ cell pool and in turn influences male fertility. FXR alpha controls the expression of the pluripotency marker Lin28 in the germ cells.
FXR signaling is a bile acid nuclear receptor that regulates lipids and glucose homeostasis and lack of it causes hepatomegaly and liver dysfunction.
These results suggest that lack of FXR impaired FoxO3a-mediated autophagy and in turn exacerbated alcohol-induced liver injury
Bile acids and salts (BA) treatment-farnesoid X-activated receptor (FRXalpha) signaling is a critical actor during sexual maturation.
deletion in liver did not protect against diet-induced steatosis
The study shows that FXR/RXR regulates Chop expression in a mouse model of steatohepatitis, providing novel insights into pathogenesis of this disorder.
alterations in bile acid composition may have contributed to the observed disturbance in FXR-mediated signalling pathways in short bowel syndrome-associated liver disease
FXR splice variant has a dominant positive effect on wild type FXR.
In conclusion, PXR and FXR both responded to ligands that activated their human orthologs, and some of the alternatively spliced variants significantly altered PXR and FXR transactivation at in vivo expression levels.
This gene encodes a ligand-activated transcription factor, which shares structural features in common with nuclear hormone receptor family, such as a DNA-binding domain that targets the receptor to specific DNA sequences, and a ligand-binding domain, which interacts directly with the ligand and contains a ligand-dependent transcriptional activation domain. This protein functions as a receptor for bile acids, and when bound to bile acids, regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.
nuclear receptor subfamily 1, group H, member 4
, orphan nuclear receptor FOR2
, bile acid receptor
, farnesoid X activated receptor
, bile acid receptor-like
, RXR-interacting protein 14
, farnesoid X nuclear receptor
, farnesoid X-activated receptor
, farnesol receptor HRR-1
, retinoid X receptor-interacting protein 14
, nuclear receptor subfamily 1 group H member 4