3-Methyladenine ameliorates liver fibrosis through autophagy regulated by the NF-κB signaling pathways on hepatic stellate cell

3-Methyladenine (3-MA) is a selective type III phosphatidylinositol 3-kinase (PI3K) inhibitor and also blocks autophagosome formation. However, the effect of 3-MA in liver fibrosis has yet to be determined. Recent studies have demonstrated that autophagy is closely related to activation of hepatic s...

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Veröffentlicht in:Oncotarget 2017-12, Vol.8 (64), p.107603-107611
Hauptverfasser: Wang, Bingying, Yang, Huan, Fan, Yinyin, Yang, Yong, Cao, Wei, Jia, Yanwei, Cao, Ying, Sun, Kangyun, Pang, Zhi, Du, Hong
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Sprache:eng
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Zusammenfassung:3-Methyladenine (3-MA) is a selective type III phosphatidylinositol 3-kinase (PI3K) inhibitor and also blocks autophagosome formation. However, the effect of 3-MA in liver fibrosis has yet to be determined. Recent studies have demonstrated that autophagy is closely related to activation of hepatic stellate cells (HSC), a process critical in the pathogenesis of liver fibrosis. And the transcription factor nuclear factor-kappaB (NF-κB) is proved to play an important role in autophagy-induced signaling pathways. Thus, inhibition of autophagy regulated by NF-κB signaling pathway in HSCs is a potential therapeutic approach for attenuating liver fibrosis. Our studies proposed that 3-MA attenuates liver fibrosis induced by carbon tetrachloride (CCl4), and inhibit the expression of autophagy markers and transcriptional regulator NF-κB of hepatic stellate cell . The function of inhibition of autophagy in activation of human hepatic stellate cell line LX-2 was blocked by the inhibitor of NF-κB . Conclusively, 3-MA ameliorates liver fibrosis through inhibition of autophagy regulated by the NF-κB signaling pathways on hepatic stellate cell.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.22539