The role and mechanism of S1PR2 in endothelial dysfunction and aortic lesions during gestational diabetes mellitus.

Authors

Lin Lu, Shan Zheng, Jianhua Li, Xinping Xie, Xiaoyun Chen, Lidan He

Published in

Placenta. Volume 183. Pages 1-13. Jul 26, 2026. Epub Jul 26, 2026.

Abstract

This study investigated the role of S1PR2 in gestational diabetes mellitus (GDM)-associated endothelial dysfunction and aortic lesions, and its relationship with advanced glycation end-products (AGEs) and the RhoA/ROCK1/eNOS pathway.
Placental tissues and serum samples were collected from patients with GDM and healthy pregnant women to assess S1PR2 expression and AGEs levels. HUVECs were treated with high glucose (HG), osmotic control medium, JTE-013, S1PR2 siRNA, S1PR2 overexpression plasmid, or AGEs-BSA. Cell viability, apoptosis, endothelial permeability, reactive oxygen species (ROS), nitric oxide (NO), and RhoA/ROCK1/eNOS pathway proteins were examined. A GDM rat model was established using a high-fat diet combined with low-dose streptozotocin, followed by pyridoxamine or JTE-013 treatment.
S1PR2 expression and serum AGEs levels were increased in GDM samples. HG impaired HUVEC viability, increased apoptosis, permeability, and ROS production, reduced NO content, activated RhoA/ROCK1 signaling, and decreased eNOS phosphorylation, while osmotic control showed no obvious effect. JTE-013 and S1PR2 knockdown alleviated endothelial injury, whereas S1PR2 overexpression aggravated these changes. AGEs-BSA upregulated S1PR2, increased ROS, and decreased NO. In GDM rats, pyridoxamine and JTE-013 reduced serum AGEs, aortic lipid deposition, vascular injury, and S1PR2/RhoA/ROCK1 pathway activation.
S1PR2 promotes high-glucose-induced endothelial dysfunction and GDM-related aortic lesions, partly through the RhoA/ROCK1/eNOS axis. AGEs may contribute to S1PR2 upregulation, suggesting that AGE formation and S1PR2 are potential targets for GDM-associated vascular injury.

PMID:
42526136
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.

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