Costunolide represses hepatic fibrosis through WW domain-containing protein 2-mediated Notch3 degradation.

ABSTRACT:

Background and purpose

This study investigates the antifibrotic activities and potential mechanisms of costunolide (COS), a natural sesquiterpene compound.

Experimental approach

Rats subjected to bile duct ligation and mice challenged with CCl₄ were used to study the antifibrotic effects of COS in vivo. Mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 also served as an in vitro liver fibrosis models. The expression of fibrogenic genes and signaling proteins in the neurogenic locus notch homologue protein 3 (Notch3)-hairy/enhancer of split-1 (HES1) pathway was examined using western blot and/or real-time PCR. Notch3 degradation was analysed using immunofluorescence and coimmunoprecipitation.

Key results

In animals, COS administration atte

SUBMITTER: Ge MX 

PROVIDER: S-EPMC6989949 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature