Conjugated secondary 12α-hydroxylated bile acids promote liver fibrogenesis.

ABSTRACT:

Background

Significantly elevated serum and hepatic bile acid (BA) concentrations have been known to occur in patients with liver fibrosis. However, the roles of different BA species in liver fibrogenesis are not fully understood.

Methods

We quantitatively measured blood BA concentrations in nonalcoholic steatohepatitis (NASH) patients with liver fibrosis and healthy controls. We characterized BA composition in three mouse models induced by carbon tetrachloride (CCl₄), streptozotocin-high fat diet (STZ-HFD), and long term HFD, respectively. The molecular mechanisms underlying the fibrosis-promoting effects of BAs were investigated in cell line models, a 3D co-culture system, and a Tgr5 (HSC-specific) KO mouse model.

Findings

We found that a group of conjuga

SUBMITTER: Xie G 

PROVIDER: S-EPMC8010625 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature