Diabetic retinopathy (DR) is a common microvascular complication that causes visual impairment or loss. Aquaporin 4 (AQP4) is a regulatory protein involved in water transport and metabolism. In previous studies, we found that AQP4 is related to hypoxia injury in Muller cells. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a non-selective cation channel protein involved in the regulation of a variety of ophthalmic diseases. However, the effects of AQP4 and TRPV4 on ferroptosis and oxidative stress in high glucose (HG)-treated Muller cells are unclear. In this study, we investigated the functions of AQP4 and TRPV4 in DR. HG was used to treat mouse Muller cells. Reverse transcription quantitative polymerase chain reaction was used to measure AQP4 mRNA expression. Western blotting was used to detect the protein levels of AQP4, PTGS2, GPX4, and TRPV4. Cell count kit-8, flow cytometry, 5,5 ' ,6,6 ' -tetrachloro-1,1,3,3 ' -tetraethylbenzimidazolyl carbocyanine iodide staining, and glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) kits were used to evaluate the function of the Muller cells. Streptozotocin was used to induce DR in rats. Haematoxylin and eosin staining was performed to stain the retina of rats. GSH, SOD, and MDA detection kits, immunofluorescence, and flow cytometry assays were performed to study the function of AQP4 and TRPV4 in DR rats. Results found that AQP4 and TRPV4 were overexpressed in HG-induced Muller cells and streptozotocin-induced DR rats. AQP4 inhibition promoted proliferation and cell cycle progression, repressed cell apoptosis, ferroptosis, and oxidative stress, and alleviated retinal injury in DR rats. Mechanistically, AQP4 positively regulated TRPV4 expression. Overexpression of TRPV4 enhanced ferroptosis and oxidative stress in HG-treated Muller cells, and inhibition of TRPV4 had a protective effect on DR-induced retinal injury in rats. In conclusion, inhibition of AQP4 inhibits the ferroptosis and oxidative stress in Muller cells by downregulating TRPV4, which may be a potential target for DR therapy.
基金：
Department of Technology Application and Development of Yunnan Province [2014RA070]; Associated Project of Yunnan Province Science and Technology Department and Kunming Medical University [202401AY070001-133]; Department of Technology Application and Development of Yunnan Province (China) [2014RA070]; Associated Project of Yunnan Province Science and Technology Department and Kunming Medical University (China) [202401AY070001-133]
第一作者机构：[1]First Peoples Hosp Yunnan Prov, Dept Ophthalmol, Kunming 650032, Yunnan, Peoples R China[2]Kunming Univ Sci & Technol, Affiliated Hosp, Kunming 650032, Yunnan, Peoples R China[*1]Department of Ophthalmology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan, China.
通讯作者：
通讯机构：[1]First Peoples Hosp Yunnan Prov, Dept Ophthalmol, Kunming 650032, Yunnan, Peoples R China[2]Kunming Univ Sci & Technol, Affiliated Hosp, Kunming 650032, Yunnan, Peoples R China[*1]Department of Ophthalmology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan, China.
推荐引用方式(GB/T 7714)：
Chen Zhen,Liu Bingjie,Zhou Daijiao,et al.AQP4 regulates ferroptosis and oxidative stress of Muller cells in diabetic retinopathy by regulating TRPV4[J].EXPERIMENTAL CELL RESEARCH.2024,439(1):doi:10.1016/j.yexcr.2024.114087.
APA：
Chen, Zhen,Liu, Bingjie,Zhou, Daijiao,Lei, Mingshu,Yang, Jingying...&Duan, Wenhua.(2024).AQP4 regulates ferroptosis and oxidative stress of Muller cells in diabetic retinopathy by regulating TRPV4.EXPERIMENTAL CELL RESEARCH,439,(1)
MLA：
Chen, Zhen,et al."AQP4 regulates ferroptosis and oxidative stress of Muller cells in diabetic retinopathy by regulating TRPV4".EXPERIMENTAL CELL RESEARCH 439..1(2024)
