Anti-NR1H4 (aa 224-238) polyclonal antibody

FXR is a transcription factor that affects target genes expression. It is also known as NR1H4. FXR modulates the metabolism of bile acids through enterohepatic circulation, and also involved in the metabolism of lipids, microbes. With further research, FXR has been found to be important in inflammation, cell proliferation and differentiation apoptosis, and cancer growth.

FXR is heterodimers with RXR, and interacts with multiple response elements to elicit transcription in most downstream genes. A nuclear receptor superfamily member, FXR has classical nuclear receptor atomicity, DNA binding domain (DBD), ligand binding domain (LBD), N-terminal AF-1, and C-terminal AF-2. AF-1 is transcriptional activation domain, AF-2 is transcriptional activation domain, ligand is involved. The FXR is also found in liver, heart, kidney and small intestine among other organs and tissues. The receptor is a cross-species evolutionarily conserved protein and NR1H4 gene has four subtypes. Bile acids trigger FXR. Bile acids cholic acid and chenodeoxycholic acid are FXR activators; ursodeoxycholic acid is antagonist, not activator.

Figure 1. Schematic diagram of four FXR-alpha protein isoforms
(Source: Jiang L, et al. 2021)

Cholesterol is converted to bile acids in the liver through both standard and non-standard routes. Primary liver bile acids are mixed with glycine or taurine to create conjugated bile acids that are sent up bile ducts by the bile salt export pump (BSEP) located on hepatocyte apical membranes and deposited in the gallbladder. These acids of bile flow along with bile into the duodenum lumen on the stimulation of food. Around 95% bile acids are active reabsorbed into the terminal ileum by the ASBT or IBAT on the apical surface of intestinal epithelial cells. They proceed down the organic solute transporter alpha/beta (OST alpha/beta) of the basolateral membrane to the portal vein and back to the liver, completes the enterohepatic circulation. Bile acids are natural receptor ligands for several of them, with FXR the most prominent nuclear receptor. FXR as a bile acid-binding transcription factor has been shown to regulate the synthesis, movement and digestion of bile acids. Activated FXR also causes the production of small heterodimer partner (SHP) when liver bile acid concentrations rise, and these form inhibitory complexes with liver receptor homolog-1 (LRH-1) and hepatocyte nuclear factor 4 alpha (HNF4alpha). That causes CYP8B1 and CYP7A1 genes to be inactivated and negatively feedback-reduces bile acid production. Active FXR in the ileum causes fibroblast growth factor 19 to be produced and enters the liver through the portal vein.

Anti-nuclear receptor subfamily 1, group H, member 4 (aa 224-238) polyclonal antibody
Anti-FXR (aa 224-238) polyclonal antibody
Anti-Farnesoid X receptor (aa 224-238) polyclonal antibody