microRNA‑103a regulates the calcification of vascular smooth muscle cells by targeting runt‑related transcription factor 2 in high phosphorus conditions

Abstract

Vascular calcification, such as atherosclerosis, is a serious complication of chronic kidney disease that is characterized by tunica media calcification, and has gained increasing attention from researchers. The commonly observed association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. As microRNAs (miRNAs) have a wide range of gene regulation functions, such as cell proliferation, apoptosis, stress and transdifferentiation, the current study aimed to determine whether miRNAs play a vital role in the calcification and osteoblastic differentiation of rat thoracic aorta vascular smooth muscle cells (VSMCs). Gene expression analysis was performed on seven miRNAs (miR-29a, -30b, -103a, -125b, -133a, -143 and -211) that maybe potentially involved in the differentiation of smooth muscle cells into osteoblastic cells. The results showed that the levels of miR-29a, -30b, -103a, -125b and -143 were markedly reduced in the VSMC calcification model, particularly miR-103a, whereas runt-related transcription factor 2 (RUNX2) expression was increased. Furthermore, it was found that the expression of RUNX2 was significantly decreased following the upregulation of miR-103a, and that the expression of RUNX2 was significantly increased by downregulating miR-103a in VSMCs. Therefore, it was concluded that miR-103a plays a notable role in the transdifferentiation of the VSMCs in high phosphorus-induced calcification by targeting the regulation of RUNX2, and may therefore constitute a new target for the diagnosis and treatment of vascular calcification.

EVs-miR-17-5p attenuates the osteogenic differentiation of vascular smooth muscle cells potentially via inhibition of TGF-β signaling under high glucose conditions

“…In vascular calcification, previous studies have shown that several miRNAs could play essential roles in the regulation of VSMC osteogenic differentiation. miR-223-3p may inhibit the osteogenic switch of vascular smooth muscle cells by regulating IL-6/STAT3 signaling 31 , and miR-103a may regulate the calcification of vascular smooth muscle cells by targeting the expression of Runx2 under high phosphorus conditions 32 . In the present study, we showed that miR-17-5p inhibits the TGF-β1-induced osteogenic differentiation of VSMCs by negatively modulating TGF-β RII expression.…”

Potential Roles of microRNAs for Assessing Cardiovascular Risk in Pre-Eclampsia-Exposed Postpartum Women and Offspring

“…The increased expression of miR-103-3a is important as it is able to protect cardiomyocytes from apoptosis and autophagy under hypoxia/reoxygenation by suppressing Atg5 expression and disrupting the Bcl-2-Beclin-1 interaction, which is involved in the regulation of autophagy [118]. RUNX2, a transcription factor for osteogenesis, increases its expression in calcified atherosclerotic plaques and plays an important role in vascular calcification [119]. However, He et al found that upregulation of miR-103a is able to reduce the expression of RUNX2, indicating the important function of this miRNA in preventing calcification in blood vessels [119].…”

“…RUNX2, a transcription factor for osteogenesis, increases its expression in calcified atherosclerotic plaques and plays an important role in vascular calcification [119]. However, He et al found that upregulation of miR-103a is able to reduce the expression of RUNX2, indicating the important function of this miRNA in preventing calcification in blood vessels [119].…”

D-box-binding protein alleviates vascular calcification in rats with chronic kidney disease by activating microRNA-195-5p and downregulating cyclin D1

“…Furthermore, microRNAs (miR) possess the ability to control cell growth, death, stress response, and transformation. They also significantly impact the calcification process and the differentiation of VSMCs into osteoblasts in the thoracic aorta of rats [ 9 ]. miR-195-5p was found to be aberrantly expressed in CKD patients with VC [ 10 ].…”