3-Methyladenine ameliorates liver fibrosis through autophagy regulated by the NF-κB signaling pathways on hepatic stellate cell
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Bingying Wang1,*, Huan Yang1,*, Yinyin Fan1, Yong Yang1, Wei Cao1, Yanwei Jia1, Ying Cao1, Kangyun Sun2, Zhi Pang3 and Hong Du1
1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P. R. China
2Department of Cardiology, The North District of Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou, Jiangsu 215008, P. R. China
3Department of Gastroenterology, The North District of Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou, Jiangsu 215008, P. R. China
*These authors contributed equally to this work
Hong Du, email: firstname.lastname@example.org
Zhi Pang, email: email@example.com
Keywords: liver fibrosis; hepatic stellate cell; 3-Methyladenine; autophagy; nuclear factor-kappaB
Received: September 18, 2017 Accepted: October 29, 2017 Published: November 20, 2017
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 in vivo. The function of inhibition of autophagy in activation of human hepatic stellate cell line LX-2 was blocked by the inhibitor of NF-κB in vitro. Conclusively, 3-MA ameliorates liver fibrosis through inhibition of autophagy regulated by the NF-κB signaling pathways on hepatic stellate cell.
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