11Beta-hydroxysteroid dehydrogenase-1 deficiency or inhibition enhances hepatic myofibroblast activation in murine liver fibrosis.

ABSTRACT: A hallmark of chronic liver injury is fibrosis, with accumulation of extracellular matrix orchestrated by activated hepatic stellate cells (HSCs). Glucocorticoids limit HSC activation in vitro, and tissue glucocorticoid levels are amplified by 11beta-hydroxysteroid dehydrogenase-1 (11βHSD1). Although 11βHSD1 inhibitors have been developed for type 2 diabetes mellitus and improve diet-induced fatty liver in various mouse models, effects on the progression and/or resolution of liver injury and consequent fibrosis have not been characterized. We have used the reversible carbon tetrachloride-induced model of hepatocyte injury and liver fibrosis to show that in two models of genetic 11βHSD1 deficiency (global, Hsd11b1^-/- , and hepatic myofibroblast-specific, Hsd11b1^fl/fl /

SUBMITTER: Zou X 

PROVIDER: S-EPMC6001805 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature