Proliferation of vascular smooth muscle cells under inflammation is regulated by NF-κB p65/microRNA-17/RB pathway activation

Abstract

Inflammation and excessive proliferation of vascular smooth muscle cells (VSMCs) have key roles in various vascular disorders, including restenosis, atherosclerosis and pulmonary artery hypertension. However, the underlying mechanism remains unclear. The present study investigated the role of nuclear factor-κB (NF-κB) and microRNA (miRNA) in the regulation of VSMC proliferation under inflammatory conditions. It was demonstrated that miR-17 stimulated the proliferation of VSMCs, enhanced cell cycle G1/S transition, and increased levels of proliferating cell nuclear antigen and E2F1. By directly targeting the retinoblastoma (RB) protein mRNA-3′ untranslated region, miR-17 suppressed the expression of RB. Activation of NF-κB p65 resulted in increased miR-17 expression in VSMCs, whereas inactivation of NF-κB p65 resulted in decreased expression of miR-17 in VSMCs. NF-κB p65 signalling directly regulates miR-17 promoter activity. NF-κB p65 activation also suppressed RB expression, which was abrogated by miR-17 inhibitor. Taken together, the present results indicated that VSMC proliferation is regulated by activation of the NF-κB p65/miR-17/RB pathway. As NF-κB p65 signalling is activated in and is a master regulator of the inflammatory response, the present findings may provide a mechanism for the excessive proliferation of VSMCs under inflammation during vascular disorders and may identify novel targets for the treatment of vascular diseases.

Determinants of circulating microRNA‐125b, a risk predictor of vascular calcification, among community‐dwelling older adults*

“…Higher RDW is frequently driven by occult inflammation, an occult modulator of miRNA expressions in vascular cells. 10 These evidences support the notion that they modify circulating miR-125b levels through altering their expressions in different tissues (Figure 2). miR-125b have been repeatedly shown to be pathogenetically important in vascular remodeling during CKD, especially VC.…”

Sunitinib-suppressed miR-452-5p facilitates renal cancer cell invasion and metastasis through modulating SMAD4/SMAD7 signals

“…According to early reports, P65, the central component of NF-КB pathway, had been suggested to act as a transcription factor in various kinds of diseases [ 30 – 33 ]. Dong Yang et al identified that P65 induced miR-17 transcription by binding its promoter elements to regulate proliferation of vascular smooth muscle cells under inflammation [ 34 ]. Rezapour S et al reported that P65 was constitutively activated in colorectal cancer [ 30 ].…”

MiR‐370 inhibits vascular inflammation and oxidative stress triggered by oxidized low‐density lipoprotein through targeting TLR4

“…21 MiR-26a can contribute to the PDGF-BB-triggered phenotypic switch of vascular smooth muscle cells by inhibiting Smad1. 22 MiR-362-3p can restrain vascular smooth muscle cell proliferation by targeting ADAMTS1 in atherosclerosis. 23 It has been indicated that miR-370 is involved in coronary artery disease.…”