Knockout of the tachykinin receptor 1 in the Mdr2-/- mouse model of primary sclerosing cholangitis reduces biliary damage and liver fibrosis.

Knockout of the tachykinin receptor 1 in the Mdr2-/- mouse model of primary sclerosing cholangitis reduces biliary damage and liver fibrosis. Am J Pathol. 2020 Jul 23;: Authors: Ceci L, Francis H, Zhou T, Giang T, Yang Z, Meng F, Wu N, Kennedy L, Kyritsi K, Meadows V, Wu C, Liangpunsakul S, Franchitto A, Sybenga A, Ekser B, Mancinelli R, Onori P, Gaudio E, Glaser S, Alpini G Abstract Activation of the substance P (SP)/neurokinin 1 receptor (NK1R) axis triggers biliary damage/senescence and liver fibrosis in bile duct ligated (BDL) and Mdr2-/- mice through enhanced transforming growth factor-β1 (TGF-β1) biliary secretion. Recent evidence indicates a role for microRNA (miR)-31 in TGF-β1-induced liver fibrosis. We aimed to define the role of the SP/NK1R/TGF-β1/miR-31 axis in regulating biliary proliferation and liver fibrosis during cholestasis. Thus, we generated a novel model with double knockout of Mdr2-/- and NK1R to further address the role of the SP/NK1R axis during chronic cholestasis. In vivo studies were performed in the following 12 wk male mice: (i) NK1R-/-; (ii) Mdr2-/-; (iii) NK1R-/-/Mdr2-/- and their corresponding wild-type (WT) controls. Liver tissues and cholangiocytes were collected and we evaluated for liver damage, changes in biliary mass/senescence and inflammation as well as liver fibrosis by both immunohistochemistry in liver sections and qPCR. miR-31 expression was measured by qPCR in isolated cholangiocytes. ...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research