Wang Bingying, Yang Huan, Fan Yinyin, Yang Yong, Cao Wei, Jia Yanwei, Cao Ying, Sun Kangyun, Pang Zhi, Du Hong
Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P. R. China.
Department of Cardiology, The North District of Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou, Jiangsu 215008, P. R. China.
Oncotarget. 2017 Nov 20;8(64):107603-107611. doi: 10.18632/oncotarget.22539. eCollection 2017 Dec 8.
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.
3-甲基腺嘌呤（3-MA）是一种选择性III型磷脂酰肌醇3-激酶（PI3K）抑制剂，也能阻断自噬体的形成。然而，3-MA在肝纤维化中的作用尚未确定。最近的研究表明，自噬与肝星状细胞（HSC）的激活密切相关，而肝星状细胞的激活在肝纤维化发病机制中至关重要。并且转录因子核因子-κB（NF-κB）被证明在自噬诱导的信号通路中起重要作用。因此，抑制肝星状细胞中由NF-κB信号通路调节的自噬是减轻肝纤维化的一种潜在治疗方法。我们的研究表明，3-MA可减轻四氯化碳（CCl4）诱导的肝纤维化，并抑制肝星状细胞自噬标志物的表达和转录调节因子NF-κB。NF-κB抑制剂可阻断抑制自噬在人肝星状细胞系LX-2激活中的作用。总之，3-MA通过抑制肝星状细胞中由NF-κB信号通路调节的自噬来改善肝纤维化。
