Abstract
Previous studies have implicated targeting Pim-1 proto-oncogene, serine/threonine kinase (PIM1) as a preventive measure against high glucose–induced cellular stress and apoptosis. This study aimed to reveal the potential role and regulatory mechanism of PIM1 in diabetic retinopathy. Human retinal microvascular endothelial cells (hRMECs) underwent high glucose induction, and fluctuations in PIM1 levels were assessed. By overexpressing PIM1, its effects on the levels of inflammatory factors, oxidative stress indicators, migration and tube formation abilities, tight junction protein expression levels, and ferroptosis in hRMECs were identified. Afterwards, hRMECs were treated with the ferroptosis-inducing agent erastin, and the effect of erastin on the above PIM1 regulatory functions was focused on. PIM1 was downregulated upon high glucose, and its overexpression inhibited the inflammatory response, oxidative stress, cell migration, and tube formation potential in hRMECs, whereas elevated tight junction protein levels. Furthermore, PIM1 overexpression reduced intracellular iron ion levels, lipid peroxidation, and levels of proteins actively involved in ferroptosis. Erastin treatment reversed the impacts of PIM1 on hRMECs, suggesting the mediation of ferroptosis in PIM1 regulation. The current study has yielded critical insights into the role of PIM1 in ameliorating high glucose–induced hRMEC dysfunction through the inhibition of ferroptosis.
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The datasets used during the present study are available from the corresponding author on reasonable request.
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Funding
This study was supported by the National Natural Science Foundation of China (No. 82070961), Shenzhen Foundation for High-level Clinical Key Specialties of Guangdong Province (No. SZGSP014), and Shenzhen Key Medical Discipline Construction Fund (No. SZXK037).
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HX and JW contributed to conception, design, investigation, and writing; JG and MY contributed to analysis and investigation. All authors have reviewed and approved the final version.
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Xie, Hb., Guo, Jh., Yang, Mm. et al. Kinase PIM1 governs ferroptosis to reduce retinal microvascular endothelial cell dysfunction triggered by high glucose. In Vitro Cell.Dev.Biol.-Animal 60, 278–286 (2024). https://doi.org/10.1007/s11626-024-00882-7
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DOI: https://doi.org/10.1007/s11626-024-00882-7