MicroRNA‑125b inhibits the proliferation of vascular smooth muscle cells induced by platelet‑derived growth factor BB

Abstract

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) is the main cause of arteriosclerosis obliterans (ASO). The present study aimed to investigate the role of microRNA (miR)-125b on the proliferation and migration of VSMCs. Platelet-derived growth factor-BB (PDGF-BB; 20 ng/ml) was used to treat VSMCs to establish an in vitro model of ASO. VSMCs were transfected with miR-125b mimic to overexpress miR-125. Cell Counting kit-8 (CCK-8) and BrdU assays were performed to assess the proliferative ability of VSMCs, while Transwell and wound healing assays were performed to assess the migratory ability of VSMCs. Western blot and immunofluorescence analyses were performed to detect the expression levels of angio-associated migratory cell protein (AAMP) and serum response factor (SRF) in VSMCs following transfection with miR-125b mimic or inhibitor. The results demonstrated that miR-125b expression decreased following treatment with PDGF-BB, the effects of which were reversed following transfection with miR-125b mimic. According to the CCK-8 assay, the cell proliferative ability decreased by ~50% compared with the negative control (NC) group, and ~40% at day 4 based on the BrdU assay. The results of the Transwell and wound healing assays indicated that the migratory ability of VSMCs significantly decreased in the miR-125b mimic group compared with the NC group. Furthermore, western blot and immunofluorescence analyses demonstrated that AAMP and SRF expression levels decreased following transfection with miR-125b mimic compared with the NC group, the effects of which were reversed following transfection with miR-125 inhibitor. Taken together, the results of the present study suggested that miR-125b inhibits the proliferative and migratory abilities of VSMCs by regulating the expression levels of AAMP and SRF.

miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine

“…It interacts with insulin-like growth factor II ( IGF-II ) to regulate myoblast differentiation in vitro and muscle regeneration in vivo [ 116 ], and with TRAF6 to prevent atrophy [ 117 ]. It is also involved in the proliferation and migration of vascular smooth muscle cells induced by platelet-derived growth factor BB [ 118 ]. In cardiac muscles, miR-125 participates in the development of the heart in embryonic mammals (reviewed in [ 119 ]); it regulates muscle-enriched transcription factors in cardiac and skeletal myocytes [ 120 ]; it can modulate cardiac progenitor cell proliferation and migration potential [ 121 ]; and it regulates cardiomyocytes proliferation and apoptosis under oxidative stress conditions [ 122 ].…”

miR125-Centered ceRNETs in Breast Cancer. Clinical, Molecular and Ethical Aspects in Personalized Medicine

“…In the muscle, miR-125b action on insulin-like growth factor II (IGF-II) negatively regulates myoblast differentiation in vitro and muscle regeneration in vivo [81], while overexpression of miR-125b-5p protects skeletal muscle from atrophy in vitro and in vivo by targeting TRAF6 through inactivation of several ubiquitin-proteasome system (UPS)and autophagy-lysosome system (ALS)-related proteins [82]; interestingly, the same interaction between miR-125b-5p and TRAF6 plays a critical role also in allergic asthma by modulating macrophage polarization [83] and in the myocardium, where it protects from ischaemia/reperfusion injury by preventing p53-mediated apoptotic signaling and suppressing TRAF6-mediated NF-κB activation [84]. The same miR is also involved in smooth muscle phenotype [85] and in the proliferation and migration of vascular smooth muscle cells induced by platelet-derived growth factor BB by regulating the expression levels of AAMP (angio-associated migratory cell) and SRF (serum response factor) proteins [86]. Also, their role in cardiac muscle is well described in the literature.…”

MiR-125 Family in Cardiovascular and Cerebrovascular Diseases

“…In the cell model of homocysteine-induced VSMCs proliferation, miR-125b could counteract the proliferation of VSMCs by targeting DNMT3b and mediating p53 DNA methylation ( Cao et al, 2016 ). In addition, miR-125b could also inhibit the proliferation and migration of VSMCs by inhibiting the expression levels of AAMP and SRF ( Wang et al, 2021 ). The function of miR-125a on VSMCs was the same as miR-125b, and both of them could inhibit the proliferation and migration of VSMCs.…”