J Pharmacol Sci. 2026 Nov;162(3):224-231. doi: 10.1016/j.jphs.2026.09.002. Epub 2026 Sep 8.
ABSTRACT
BACKGROUND: High glucose-induced injury to human retinal endothelial cells (HRCCs) is closely associated with retinal disorders, and melatonin has potential protective effects. However, its underlying mechanism remains unclear.
METHODS: human retinal endothelial cells (HRCCs) were exposed to high glucose and treated with melatonin. Cell viability, apoptosis, and intracellular reactive oxygen species (ROS) levels were assessed using CCK-8, TUNEL staining, and DCFH-DA probe assays, respectively. The expression of PANoptosis-related proteins and components of the Hippo pathway were analyzed by Western blot. LncSNHG5 and miR-26a-5p expression were detected via RT-PCR. Luciferase reporter and RNA-pulldown assays, along with FISH, were employed to confirm direct interactions. Overexpression of LncSNHG5 and co-transfection with miR-26a-5p mimic were utilized to elucidate their roles.
RESULTS: Melatonin dose-dependently improved HRCC viability, inhibited apoptosis, ROS accumulation and PANoptosis-related proteins (N-GSDMD, p-MLKL, p-RIP3) expression induced by high glucose. High glucose upregulated LncSNHG5, which was dose-dependently downregulated by melatonin. LncSNHG5 directly interacted with miR-26a-5p, and melatonin regulated the Hippo pathway (LATS1/YAP phosphorylation) and PANoptosis via the LncSNHG5/miR-26a-5p axis. Overexpression of LncSNHG5 reversed melatonin's protective effects, which was attenuated by miR-26a-5p mimic.
CONCLUSION: Melatonin alleviates high glucose-induced HRCC injury by regulating PANoptosis, ROS accumulation and Hippo pathway via the LncSNHG5/miR-26a-5p axis.
PMID:42810779 | DOI:10.1016/j.jphs.2026.09.002