PGK1 Regulates Oxidative Stress in Gestational Diabetes Mellitus through the Estradiol-Keap1-Nrf2 Pathway.

ABSTRACT: Gestational diabetes mellitus (GDM), the most common pregnancy-related metabolic disorder, is characterized by exacerbated oxidative stress (OS). The inhibition of phosphoglycerate kinase 1 (PGK1), the first ATP-generating enzyme in the glycolytic pathway, activates Keap1-Nrf2 antioxidant pathways and reduces OS. However, the detailed roles of PGK1 in GDM remain unexplored. Disruption of pro-oxidant/antioxidant homeostasis was observed in the placentas of GDM patients. PGK1 was significantly upregulated in both human GDM placentas and streptozotocin (STZ)-induced model mice. Pharmacological inhibition of PGK1 in vivo ameliorated placental dysfunction, attenuated excessive ROS production, and improved pregnancy outcomes. Lentivirus-mediated PGK1 knockdown in HTR8/SVneo trophoblasts i

SUBMITTER: Peng Y 

PROVIDER: S-EPMC12435576 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature