Gigantol protects retinal pigment epithelial cells against high glucose-induced apoptosis, oxidative stress and inflammation by inhibiting MTDH-mediated NF-kB signaling pathway

ObjectiveAs a frequent complication of diabetes mellitus (DM), diabetic retinopathy (DR) is now one of the major causes of blindness. Recent reports have shown that retinal pigment epithelial cell (RPEC) damage plays an essential part in DR development and progression. This work intended to explore the potential effects of Gigantol on high glucose (HG)-stimulated RPEC damage and identify potential mechanisms.MethodsCell viability, cell damage, and cell apoptosis were evaluated by CCK-8, lactate dehydrogenase (LDH) and flow cytometry assays. The levels of oxidative stress biomarkers and pro-inflammatory cytokines were assessed using corresponding commercial kits and ELISA. Additionally, the levels of MTDH and NF-kB signaling pathway-related proteins were detected by western blotting.ResultsGigantol dose-dependently enhanced cell viability and decreased apoptosis in HG-challenged ARPE-19 cells. Also, Gigantol notably relieved oxidative stress and inflammatory responses in ARPE-19 cells under HG conditions. Gigantol dose-dependently suppressed MTDH expression. In addition, MTDH restoration partially counteracted the protective effects of Gigantol on ARPE-19 cells subject to HG treatment. Mechanically, Gigantol inactivated the NF-kB signaling pathway, which was partly restored after MTDH overexpression.ConclusionOur findings suggested that Gigantol protected against HG-induced RPEC damage by inactivating the NF-kB signaling via MTDH inhibition, offering a potent therapeutic drug for DR treatment.

Automated summary

The study aimed to investigate the potential effects of Gigantol on high glucose-stimulated retinal pigment epithelial cell (RPEC) damage and identify the underlying mechanisms. The results showed that Gigantol protected against HG-induced RPEC damage by inhibiting MTDH and inactivating the NF-kB signaling pathway, offering a potential therapeutic drug for diabetic retinopathy treatment.