MiR-155-5p Attenuates Vascular Smooth Muscle Cell Oxidative Stress and Migration via Inhibiting BACH1 Expression

Abstract

The malfunction of vascular smooth muscle cells (VSMCs) is an initiating factor in the pathogenesis of pathological vascular remodeling, including hypertension-related vascular lesions. MicroRNAs (miRNAs) have been implicated in the pathogenesis of VSMC proliferation and migration in numerous cases of cardiovascular remodeling. The evidence for the regulatory role of miR-155-5p in the development of the cardiovascular system has been emerging. However, it was previously unclear whether miR-155-5p participated in the migration of VSMCs under hypertensive conditions. Thus, we aimed to define the exact role and action of miR-155-5p in VSMC migration by hypertension. Here, we detected that the level of miR-155-5p was lower in primary VSMCs from spontaneously hypertensive rats (SHRs). Its overexpression attenuated, while its depletion accelerated, the migration and oxidative damage of VSMCs from SHRs. Our dual-luciferase reporter assay showed that miRNA-155-5p directly targeted the 3′-untranslated region (3′-UTR) of BTB and CNC homology 1 (BACH1). The miR-155-5p mimic inhibited BACH1 upregulation in SHR VSMCs. By contrast, the deletion of miR-155-5p further elevated the upregulation of BACH1 in SHR-derived VSMCs. Importantly, the overexpression of miR-155-5p and knockdown of BACH1 had synergistic effects on the inhibition of VSMCs in hypertension. Collectively, miR-155-5p attenuates VSMC migration and ameliorates vascular remodeling in SHRs, via suppressing BACH1 expression.

Extracellular vesicle-mediated transfer of BACH1 from macrophage promotes vascular smooth muscle cell proliferation via suppressing FNDC5 expression

“…Our previous research has been shown that BACH1 facilitates VSMC migration [21]. In the present study, we found that the content and level of BACH1 in EVs of SHRs were much higher than that of WKYs.…”

“…Recently, we have found that miR-155-5p attenuates VSMC oxidative stress and migration via inhibiting BTB and CNC homology1 (BACH1) expression [21], which increases in the EVs from macrophages of spontaneously hypertensive rats (SHRs), compared with that of Wistar-Kyoto rat (WKYs). BACH1, as a stress-reactive transcription factor, can enhance oxidative stress, regulate cell cycle and immune function [22].…”

Integrative analysis of the lncRNA-miRNA-mRNA interactions in smooth muscle cell phenotypic transitions

“…Also, in non-small cell lung cancer (NSCLC) tissues, miR-196a was significantly upregulated, which in turn resulted in NSCLC cell migration and invasion, partially via downregulation of HOXA5 (Liu et al, 2012), and miR-155 has been implicated in with inflammation and cardiovascular diseases (Schroen and Heymans, 2012). In addition, previous reports characterized miR-155 and miR-122 as suppressors of cell migration and oxidative stress, including vascular SMC (Tong et al, 2023), whereas knockdown of miR-155-5p results in increased proliferation and migration of human brain micro-vessel ECs (Liu et al, 2015). Another significantly Schematic showing regulatory mechanisms obtained from the integrative analysis of the lncRNA-miRNA-mRNA interactions in OCT4 deficient SMCs.…”

PCR Array Profiling of miRNA Expression Involved in the Differentiation of Amniotic Fluid Stem Cells toward Endothelial and Smooth Muscle Progenitor Cells

“…Finally, overexpression of miR-155-5p and downregulation of BACH1 repressed the migration of VSMCs. The suppression of BACH1 by miR-155-5p was sufficient to decrease the migration and oxidative stress in VSMCs [ 37 ]. A recent study published by Li et al using a knock-out model of miR-214 in VSMCs investigated the role of miR-214 in vascular smooth muscle cells by quantification of the expression of contractile markers including smooth muscle actin, smooth muscle myosin heavy chain, and calponin.…”