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

• Published in: Molecular biology reports Vol. 50; no. 11; pp. 9073 - 9083
• Main Authors: Elshamy, Amira M., Hafez, Yasser Mostafa, Safa, Mohamed A. E., Ibrahim, Hoda A., Khalfallah, Mohamed, Rizk, Fatma H., Eltabaa, Eman F., Ghafar, Muhammad T. Abdel, Atef, Marwa Mohamed
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.11.2023; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; beta Catenin - genetics; beta Catenin - metabolism; Biomedical and Life Sciences; Calcification; Calcification (ectopic); Cardiovascular diseases; Cbfa-1 protein; Chromosome 3; Core Binding Factor Alpha 1 Subunit - genetics; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Dkk1 protein; Down-regulation; Epigenetics; Gene expression; Histology; Humans; Life Sciences; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Morphology; Original Article; Osteoprotegerin; Osteoprotegerin - genetics; Osteoprotegerin - metabolism; Signal transduction; Signal Transduction - genetics; TRANCE protein; Vascular Calcification - genetics; Vascular Calcification - metabolism; Wnt protein; β-Catenin; Vascular calcification; Dickkopf-1; RANKL; WNT/β-Catenin pathway; miR-433-3p; Osteoprotegerin
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-08792-9

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.