Troubles immunologiques et immunothérapie
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Abstrait

Curcumol Targets Gls1 to Regulate Glutamine Metabolism and Induce Senescence of Hepatic Stellate Cells to Exert Anti-Hepatic Fibrosis Mechanism

Xuelin Duan*, Tiejian Zhao, Jiaru Wang, Jiahui Wang, Yang Zheng

Objective: Curcuma has long been used as a Chinese herbal medicine for the treatment of chronic liver disease, and curcumol is its main active ingredient. This study explores the molecular mechanism of curcumol regulating glutamine metabolism, hoping to provide new ideas for the prevention and treatment of chronic liver disease.

Methods: We used LPS to activate hepatic stellate cells. The effects of curcumol on glutamine metabolism and cell proliferation were detected by kit. The effects of curcumol on GLS1, senescence-related proteins and extracellular matrix expression were observed by Western blotting and RT-PCR. The effect of curcumol on cell cycle was detected by flow cytometry. Furthermore, after overexpression of GLS1, we observed the effects of curcumol on glutamine metabolism, expression of related molecules and cell cycle.

Results: Curcumol significantly inhibited cell proliferation, glutamine metabolism, GLS1 and extracellular matrix expression, and significantly promoted cell senescence. When we further over express GLS1, the inhibitory effect of curcumol on glutamine metabolism and the effect of promoting cell senescence were also saved.

Conclusions: Curcumol targets GLS1, inhibits glutamine metabolism and induces senescence of hepatic stellate cells, which may be one of the important mechanisms of its anti-hepatic fibrosis. GLS1 may be an important target site for the prevention and treatment of chronic liver disease.