Hypoxia induces the activation of hepatic stellate cells through the PVT1-miR-152-ATG14 signaling pathway

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 a...

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Published in:Molecular and cellular biochemistry 2020-02, Vol.465 (1-2), p.115-123
Main Authors: Yu, Fujun, Dong, Buyuan, Dong, Peihong, He, Yanghuan, Zheng, Jianjian, Xu, Ping
Format: Article
Language:English
Subjects:
Animals
Autophagic Cell Death
Autophagy
Autophagy-Related Proteins - metabolism
Biochemistry
Biomedical and Life Sciences
Cardiology
Cell activation
Cell Hypoxia
Fibrosis
Hepatic Stellate Cells - metabolism
Hepatic Stellate Cells - pathology
Hypoxia
Kinases
Life Sciences
Liver
Liver Cirrhosis - metabolism
Liver Cirrhosis - pathology
Luciferase
Lymphomas
Medical Biochemistry
Mice
MicroRNAs - metabolism
Oncology
Phagocytosis
Plasmacytoma
RNA, Long Noncoding - metabolism
Signal Transduction
Signaling
siRNA
Stellate cells
Translocation
Vesicular Transport Proteins - metabolism
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Summary: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 2 . Taken together, autophagy induction via the PVT1-miR-152-ATG14 signaling pathway contributes to activation of HSCs under hypoxia condition.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-019-03672-y