Inhibition of 11β-hydroxysteroid dehydrogenase 1 relieves fibrosis through depolarizing of hepatic stellate cell in NASH.

ABSTRACT: 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. Although 11βHSD1 has been implicated in numerous metabolic syndromes, such as obesity and diabetes, the functional roles of 11βHSD1 during progression of nonalcoholic steatohepatitis (NASH) and consequent fibrosis have not been fully elucidated. We found that pharmacological and genetic inhibition of 11βHSD1 resulted in reprogramming of hepatic stellate cell (HSC) activation via inhibition of p-SMAD3, α-SMA, Snail, and Col1A1 in a fibrotic environment and in multicellular hepatic spheroids (MCHSs). We also determined that 11βHSD1 contributes to the maintenance of NF-κB signaling through modulation of TNF, TLR7, ITGB3, and TWIST, as w

SUBMITTER: Lee SY 

PROVIDER: S-EPMC9709168 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature