P4ha2-flox Mouse

P4ha2, a subunit of prolyl-4-hydroxylases, contains a substrate binding and catalyzation domain and is a key enzyme in collagen synthesis. It is involved in multiple biological processes and signaling pathways, such as the Hippo, PI3K/AKT, and Hedgehog signaling pathways, and is of great biological importance in various physiological and pathological conditions [1,2,3,4,5]. Genetic models, especially gene knockout mouse models, are valuable for studying its functions.

In P4ha2-/-mice injured by DDC, there was a significantly reduced level of ductular reaction and fibrosis compared with controls in the DDC-induced chronic cholestasis. Also, decreased liver fibrosis and ductular reaction were observed in P4ha2-/-/MDR2-/-mice compared with MDR2-/-mice. Cholangiocytes isolated from P4ha2-/-/MDR2-/-mice displayed a higher level of YAP phosphorylation, resulting in cholangiocytes proliferation inhibition. This shows that P4ha2 promotes hepatic ductular reaction and biliary fibrosis by regulating the SAV1-mediated Hippo signaling pathway, indicating its potential as a therapeutic target for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) [1].

In conclusion, P4ha2 plays crucial roles in processes like collagen synthesis and regulation of multiple signaling pathways. The study of P4ha2 knockout mouse models has revealed its significant impact on biliary fibrosis and related cholestatic liver diseases, providing insights into potential therapeutic strategies for PBC and PSC.