microRNA-203 Targets Insulin-Like Growth Factor Receptor 1 to Inhibit Trophoblast Vascular Remodeling to Augment Preeclampsia

Am J Perinatol. 2024 Feb;41(3):355-364. doi: 10.1055/s-0041-1740300. Epub 2021 Dec 10.

Abstract

Objective: Preeclampsia (PE) is a pregnancy-specific condition featured by high blood pressure, edema, and proteinuria. Research about the role of microRNA (miR)-203 in PE remains insufficient. This experiment is designed to investigate the specific role of miR-203 in trophoblasts in PE.

Study design: miR-203 expression in placenta tissues of normal pregnant women and PE patients was examined to analyze the relevance between miR-203 and PE diagnostic efficiency and between miR-203 and blood pressure (systolic pressure and diastolic pressure) and proteinuria of PE patients. miR-203 expression was downregulated in hypoxia-cultured trophoblasts using miR-203 inhibitor to assess matrix metalloproteinase-9 (MMP-9) level. Then, the angiogenesis of trophoblasts with different treatments was determined. Subsequently, the target relation between miR-203 and insulin-like growth factor receptor 1 (IGF-1R) was predicted and verified. Additionally, the effect of IGF-1R in the mechanism of miR-203 modulating trophoblast vascular remodeling was detected.

Results: miR-203 was overexpressed in the placenta of PE patients and it acted as a promising diagnostic indicator for PE. Moreover, miR-203 was positively associated with blood pressure (systolic pressure and diastolic pressure) and proteinuria of PE patients. miR-203 silencing in hypoxia-cultured trophoblasts enhanced trophoblast vascular remodeling. Mechanically, miR-203 bound to IGF-1R to suppress its transcription. IGF-1R downregulation counteracted the promotive effect of miR-203 silencing on trophoblast vascular remodeling.

Conclusion: miR-203 was overexpressed in PE, and it targeted IGF-1R to limit trophoblast vascular remodeling.

Key points: · miR-203 is overexpressed in the placenta of PE patients.. · miR-203 acts as a potential diagnostic marker for PE.. · miR-203 targets IGF-1R to reduce trophoblast vascular remodeling in PE..

MeSH terms

  • Female
  • Humans
  • Hypoxia / metabolism
  • Insulin-Like Peptides
  • MicroRNAs* / metabolism
  • Placenta / metabolism
  • Pre-Eclampsia* / metabolism
  • Pregnancy
  • Proteinuria / metabolism
  • Trophoblasts / metabolism
  • Vascular Remodeling

Substances

  • Insulin-Like Peptides
  • MicroRNAs
  • MIRN203 microRNA, human