PGK1 Regulates Oxidative Stress in Gestational Diabetes Mellitus through the Estradiol-Keap1-Nrf2 Pathway
Year: 2025
Type: article
Abstract: ameliorated placental dysfunction, attenuated excessive ROS production, and improved pregnancy outcomes. Lentivirus-mediated PGK1 knockdown in HTR8/SVneo trophoblasts increased Nrf2-dependent antioxidant protein expression while reducing ROS generation. Mechanistically, PGK1 inhibition elevated estradiol levels, facilitating Keap1 dimerization, and this dimerization destabilized the Keap1-Nrf2 complex, enabling Nrf2 accumulation and antioxidant activation. Exogenous estradiol supplementation recapitulated the effect of inhibiting PGK1 by enhancing Keap1 dimer formation, effectively mitigating placental OS and adverse pregnancy phenotypes in GDM models. This study elucidates the critical role of PGK1 in restoring redox homeostasis through the estradiol-Keap1-Nrf2 axis in the pathogenesis of GDM. PGK1/estradiol crosstalk represents a druggable target, and pharmacological PGK1 inhibition has translational potential for mitigating oxidative stress-related pregnancy complications.
DOI: 10.7150/ijbs.113728
Authors: You Peng, Hengli Zhao, Jun Chen, Chi Chiu Wang, Tao Zhang, Tsz Ching Yeung, Haotong Ouyang, Jiayu Zhu, Xiangli Chen, Meng Li, Haoyue Hu, Mei Zhong
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,337
OpenAlex ID: W4414205162