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STEAP4 Inhibits HIF-1α/PKM2 Signaling and Reduces High Glucose-Induced Apoptosis of Retinal Vascular Endothelial Cells

Authors Liu L, Xu H, Zhao H, Jiang C

Received 27 February 2020

Accepted for publication 29 April 2020

Published 20 July 2020 Volume 2020:13 Pages 2573—2582

DOI https://doi.org/10.2147/DMSO.S251663

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Juei-Tang Cheng


Lei Liu,1 Hui Xu,1 Hongyu Zhao,2 Chunying Jiang1

1Department of Ophthalmology, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China; 2Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China

Correspondence: Chunying Jiang
Department of Ophthalmology, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, People’s Republic of China
Email jiangchunying2020@163.com

Background: Diabetic retinopathy (DR) is a vascular lesion induced by high glucose. STEAP4 is an indispensable membrane protein, which is closely related to hyperglycemic-induced cell inflammation and injury, while STEPT4 has not been studied in hyperglycemic-induced retinal vascular endothelial cell injury.
Methods: The expression of STEAP4 was detected by RT-qPCR and Western blot. CCK-8 was used to detect cell survival. STEAP4 was overexpressed by cell transfection. The expressions of cytokines TNF-α, IL-1, IL-6, ICAM-1, MDA, SOD and ROS were detected by ELISA. Cell apoptosis was detected by flow cytometry. The expressions of proteins associated with cell damage VEGF, KLF2, eNOS and apoptosis-related proteins Bax, cleaved caspase3 and Bcl2 were detected by Western blot. Finally, the expressions of HIFα and PKM2 were detected by immunofluorescence and Western blot.
Results: The expression of STEAP4 in hyperglycemic-induced retinal vascular endothelial cells (HRCECs) decreased gradually. Overexpression of STEAP4 reduced inflammation and apoptosis of HRCECs and improved dysfunction of them. Meanwhile, overexpression of steap4 inhibited the expression of HIF-1α/PKM2 signal.
Conclusion: STEAP4 can be a potential therapeutic target for diabetic retinopathy by inhibiting HIF1/PKM2 signaling to reduce hyperglycemic-induced retinal cell apoptosis.

Keywords: diabetic retinopathy, STEAP4, HIF-1α/PKM2, HG-induced retinal vascular endothelial cells

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