Ghrelin attenuates hypoxia-induced mitochondrial oxidative stress damage in HTR-8/SVneo trophoblasts.

BACKGROUND

Preeclampsia (PE) is a life-threatening complication of pregnancy. Hypoxia-induced mitochondrial damage, oxidative stress and apoptosis in trophoblasts are critical in PE pathogenesis. Ghrelin exerts protective effects in multiple tissues, but its role and mechanism in hypoxic trophoblasts remain unclear.

METHODS

HTR-8/SVneo cells were divided into 8 groups: normoxia, normoxia + 1000 nmol/L D-Lys3-GHRP-6, hypoxia, hypoxia + 1000 nmol/L D-Lys3-GHRP-6, hypoxia + 1, 10, 100, 1000 nmol/L Ghrelin. Mitochondrial ultrastructure was observed by TEM. ROS, MDA, SOD, CAT, GPX4 and apoptosis were detected. Bioinformatics and Western blotting were used to screen and validate proteins. TGFB2 was silenced to verify its mediating role in ghrelin-induced protection.

RESULTS

Hypoxia induced mitochondrial swelling, cristae rupture, ROS accumulation, increased MDA, reduced antioxidant enzyme activities and enhanced apoptosis. Ghrelin mitigated these injuriesin a dose-dependent manner, with optimal effect at 1000 nmol/L. Bioinformatics and Western blotting identified TGFB2 as a key target upregulated by hypoxia and downregulated by Ghrelin. TGFB2 knockdown mimicked Ghrelin-mediated protection.

CONCLUSION

Ghrelin protects trophoblasts against hypoxia-induced mitochondrial damage, oxidative stress and apoptosis. This study uncovers a novel mechanism and provides a potential therapeutic target for PE intervention.