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

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 d ouble knockout of Mdr2-/- and NK1R to further address the role of the SP/NK1R axis during chronic cholestasis.

Source: American Journal of Pathology - July 21, 2020 Category: Pathology Authors: Ludovica Ceci, Heather Francis, Tianhao Zhou, Thao Giang, Zhihong Yang, Fanyin Meng, Nan Wu, Lindsey Kennedy, Konstantina Kyritsi, Vik Meadows, Chaodong Wu, Suthat Liangpunsakul, Antonio Franchitto, Amelia Sybenga, Burcin Ekser, Romina Mancinelli, Paolo O Tags: Regular Article Source Type: research