Hypoxia Induces the Activation of Hepatic Stellate Cells Through the PVT1-miR-152-ATG14 Signaling Pathway

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2020 Jan 2

PMID 31893334

Citations 17

Authors

Fujun Yu

Buyuan Dong

Peihong Dong

Yanghuan He

Jianjian Zheng

Ping Xu

Affiliations

Soon will be listed here.

Abstract

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% O. Taken together, autophagy induction via the PVT1-miR-152-ATG14 signaling pathway contributes to activation of HSCs under hypoxia condition.

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