期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 383, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2023.110673
关键词
Ferroptosis; Glycolysis; Hepatic stellate cells; Liver fibrosis; TUG1
The study revealed that the TUG1 molecule, mediated by glycolysis regulator PDK4, plays an important regulatory role in liver fibrosis. By promoting glycolysis and inhibiting ferroptosis in hepatic stellate cells, it contributes to the progression of liver fibrosis.
The induction of ferroptosis in hepatic stellate cells (HSCs) has shown promise in reversing liver fibrosis. And ferroptosis has been confirmed to be associated with glycolysis. The objective of this study is to determine whether ferroptosis inhibition in HSCs, induced by elevation of recombinant pyruvate dehydrogenase kinase isozyme 4 (PDK4)-mediated glycolysis, could mediate the pathogenesis of liver fibrosis. Liver fibrosis was induced using CCl4, the level of which was assessed through histochemical staining. Lentivirus was used to modulate the expression of specific genes. And underlying mechanisms were explored using primary HSCs extracted from normal mice. The results confirmed that Taurine up-regulated gene 1 (TUG1) expression was upregulated in liver fibrotic tissues and HSCs, showing a positive correlation with fibrosis. In addition, TUG1 attenuated ferroptosis in HSCs by promoting PDK4-mediated glycolysis, thereby promoting the progression of liver fibrosis. Moreover, TUG1 was observed to impact HSCs activation, exacerbating liver fibrosis to some extent. In conclusion, our study revealed that TUG1 expression was elevated in mouse models of liver fibrosis and activated HSCs, which inhibited ferroptosis in HSCs through PDK4-mediated glycolysis. This finding may open up a new therapeutic strategy for liver fibrosis.
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