The role of miR-433-3p in vascular calcification in type 2 diabetic patients: targeting WNT/β-Catenin and RANKL/RANK/OPG signaling pathways

Mol Biol Rep. 2023 Nov;50(11):9073-9083. doi: 10.1007/s11033-023-08792-9. Epub 2023 Sep 20.

Abstract

Background: Vascular calcification (VC) is a major predictor of cardiovascular diseases that represent the principal cause of mortality among type-2 diabetic patients. Accumulating data suggest the vital role of some microRNAs on vascular calcification as an epigenetic regulator. Thus, we assessed herein, the role of serum miR-433-3p in vascular calcification in type-2 diabetic patients.

Methods: Twenty healthy subjects (control group) and forty diabetic patients (20 without VC and 20 with VC) were involved in the study. miR-433-3p gene expression was measured. Runx2, Dickkopf-1 (DKK1), β-catenin, Receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) levels in serum were assessed by ELISA technique.

Results: Diabetes patients had significantly lower levels of miR-433-3p expression in comparison to the control group, with the lowest levels being found in diabetic patients with VC. Furthermore, Runx2, β-catenin, and RANKL levels were significantly increased with concomitant lower DKK1 and OPG levels detected in the two diabetic groups especially those with VC.

Conclusion: Collectively, the study documented that down-regulation of miR-433-3p may contribute to the development of VC through activating WNT/β-Catenin and RANKL/RANK/OPG signaling pathways.

Keywords: Dickkopf-1; Osteoprotegerin; RANKL; Vascular calcification; WNT/β-Catenin pathway; miR-433-3p.

MeSH terms

  • Core Binding Factor Alpha 1 Subunit / genetics
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism
  • Signal Transduction / genetics
  • Vascular Calcification* / genetics
  • Vascular Calcification* / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Osteoprotegerin
  • Core Binding Factor Alpha 1 Subunit
  • beta Catenin
  • MicroRNAs
  • MIRN433 microRNA, human