Oncotarget

Research Papers:

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

Bingying Wang, Huan Yang, Yinyin Fan, Yong Yang, Wei Cao, Yanwei Jia, Ying Cao, Kangyun Sun, Zhi Pang and Hong Du _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:107603-107611. https://doi.org/10.18632/oncotarget.22539

Metrics: PDF 2517 views  |   HTML 3037 views  |   ?  


Abstract

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

Correspondence to:

Hong Du, email: hong_du@126.com

Zhi Pang, email: pangzhi0273@sina.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

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 22539