The Secretin/Secretin Receptor Axis Modulates Ductular Reaction and Liver Fibrosis through Changes in Transforming Growth Factor-β1-Mediated Biliary Senescence.

ABSTRACT: Activation of the secretin (Sct)/secretin receptor (SR) axis stimulates ductular reaction and liver fibrosis, which are hallmarks of cholangiopathies. Our aim was to define the role of Sct-regulated cellular senescence, and we demonstrated that both ductular reaction and liver fibrosis are significantly reduced in Sct^-/-, SR^-/-, and Sct^-/-/SR^-/- bile duct ligated (BDL) mice compared with BDL wild-type mice. The reduction in hepatic fibrosis in Sct^-/-, SR^-/-, and Sct^-/-/SR^-/- BDL mice was accompanied by reduced transforming growth factor-β1 levels in serum and cholangiocyte supernatant, as well as decreased expression of markers of cellular senescence in cholangiocytes in contrast to enhanced cellular se

SUBMITTER: Wu N 

PROVIDER: S-EPMC6168967 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature