Differentiation-inducing factor-1 prevents hepatic stellate cell activation through inhibiting GSK3β inactivation

Shohei Furukawa, Momoka Yamaguchi, Akira Ooka, Haruhisa Kikuchi, Tomohisa Ishikawa, Shin ya Saito

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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 3β (GSK3β) inhibitor, attenuated the inhibitory effect of DIF-1. Moreover, the level of inactive GSK3β (phosphorylated at Ser9) was significantly reduced by DIF-1. DIF-1 also inhibited nuclear translocation of β-catenin and reduced the level of non-phospho (active) β-catenin. These results suggest that DIF-1 inhibits HSC activation by disrupting the Wnt/β-catenin signaling pathway through dephosphorylation of GSK3β. We propose that DIF-1 is a possible candidate as a therapeutic agent for preventing liver fibrosis.

Original languageEnglish
Pages (from-to)140-144
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2019 Nov 26
Externally publishedYes


  • Differentiation-inducing factor-1
  • Glycogen synthase kinase 3β
  • Hepatic stellate cell
  • Liver fibrosis
  • Transdifferentiation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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