Elevated galectin-3 levels detected in women with hyperglycemia during early and mid-pregnancy antagonizes high glucose - induced trophoblast cells apoptosis via galectin-3/foxc1 pathway

Mol Med. 2023 Aug 25;29(1):115. doi: 10.1186/s10020-023-00707-5.

Abstract

Objective: This study was to evaluate plasma galectin-3 levels from early pregnancy to delivery and explore the effects of galectin-3 on the function of trophoblast cells under high glucose exposure.

Methods: The plasma galectin-3 levels were quantified by enzyme-linked immunosorbent assay (ELISA) in the China National Birth Cohort (CNBC) at Peking University First Hospital, and the underlying signaling pathway was identified by protein-protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), quantitative PCR (qPCR), western blotting, small interfering RNA (siRNA) transfections, and flow cytometry.

Results: Significantly higher galectin-3 levels were found in patients with gestational diabetes mellitus (GDM group; n = 77) during the first and second trimesters than that in healthy pregnant women (HP group; n = 113) (P < 0.05). No significant differences in plasma galectin-3 levels were detected between GDM and HP groups in maternal third-trimester blood and cord blood. PPI analysis suggested potential interactions between galectin-3 and foxc1. The findings of GSEA showed that galectin-3 was involved in the cytochrome P450-related and complement-related pathways, and foxc1 was associated with type I diabetes mellitus. Additionally, high glucose (25 mM) significantly increased the expression levels of galectin-3 and foxc1 and induced apoptosis in HTR-8/SVneo cells. Further in vitro experiments showed that galectin-3/foxc1 pathway could protect HTR-8/SVneo cells against high glucose - induced apoptosis.

Conclusion: Future studies were required to validate whether plasma galectin-3 might become a potential biomarker for hyperglycemia during pregnancy. Elevated galectin-3 levels might be a vital protective mechanism among those exposed to hyperglycemia during pregnancy.

Keywords: Apoptosis; Galectin-3; Gestational diabetes mellitus; Hyperglycemia in pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Female
  • Galectin 3* / genetics
  • Glucose
  • Humans
  • Hyperglycemia*
  • Pregnancy
  • Trophoblasts

Substances

  • Galectin 3
  • Glucose
  • LGALS3 protein, human