Increasing studies have indicated that hypoxia serves as a pivotal microenvironmental factor that facilitates activation of hepatic stellate cells (HSCs). However, the mechanism by which hypoxia activates HSCs is not clear. Here, we demonstrated that plasmacytoma variant translocation 1 (PVT1) and autophagy were overexpressed in liver fibrotic specimens. In primary mouse HSCs, both PVT1 and autophagy were induced by hypoxia. Further study showed that hypoxia-induced autophagy depended on expression of PVT1 and miR-152 in HSCs. Luciferase reporter assay indicated that autophagy-related gene 14 (ATG14) was a direct target of miR-152. In addition, inhibition of autophagy by 3-methyladenine and Beclin-1 siRNA impeded activation of HSCs cultured in 1% O2. Taken together, autophagy induction via the PVT1-miR-152-ATG14 signaling pathway contributes to activation of HSCs under hypoxia condition.

中文翻译：

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低氧通过PVT1-miR-152-ATG14信号传导途径诱导肝星状细胞的活化。

越来越多的研究表明，缺氧是促进肝星状细胞（HSC）活化的关键微环境因子。然而，低氧激活HSC的机制尚不清楚。在这里，我们证明浆细胞瘤变体易位1（PVT1）和自噬在肝纤维化标本中过表达。在原代小鼠HSC中，缺氧诱导PVT1和自噬。进一步的研究表明，缺氧诱导的自噬依赖于HSC中PVT1和miR-152的表达。荧光素酶报告基因测定表明自噬相关基因14（ATG14）是miR-152的直接靶标。此外，3-甲基腺嘌呤和Beclin-1 siRNA对自噬的抑制作用会阻止在1％O2中培养的HSC的活化。在一起