Differentiation-inducing factor-1 prevents hepatic stellate cell activation through inhibiting GSK3ß inactivation.
Biochem Biophys Res Commun
; 520(1): 140-144, 2019 11 26.
Article
in En
| MEDLINE
| ID: mdl-31582219
ABSTRACT
Differentiation-inducing factor-1 (DIF-1), a morphogen produced by the cellular slime mold Dictyostelium discoideum, is a natural product that has attracted considerable attention for its antitumor properties. Here, we report a novel inhibitory effect of DIF-1 on the activation of hepatic stellate cells (HSCs) responsible for liver fibrosis. DIF-1 drastically inhibited transdifferentiation of quiescent HSCs into myofibroblastic activated HSCs in a concentration-dependent manner, thus conferring an antifibrotic effect against in the liver. Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, showed any effect on the inhibition of HSC activation by DIF-1. In contrast, TWS119, a glycogen synthase kinase 3ß (GSK3ß) inhibitor, attenuated the inhibitory effect of DIF-1. Moreover, the level of inactive GSK3ß (phosphorylated at Ser9) was significantly reduced by DIF-1. DIF-1 also inhibited nuclear translocation of ß-catenin and reduced the level of non-phospho (active) ß-catenin. These results suggest that DIF-1 inhibits HSC activation by disrupting the Wnt/ß-catenin signaling pathway through dephosphorylation of GSK3ß. We propose that DIF-1 is a possible candidate as a therapeutic agent for preventing liver fibrosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatic Stellate Cells
/
Glycogen Synthase Kinase 3 beta
/
Hexanones
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2019
Document type:
Article
Affiliation country: