MicroRNA-212-5p and its target PAFAH1B2 suppress vascular proliferation and contraction via the downregulation of RhoA

Abstract

Vascular remodeling and contraction contribute to the development of hypertension. We investigated the role of miR-212-5p and its downstream target in vascular smooth muscle cell (VSMC) proliferation, migration, and contraction. MicroRNA microarray and PCR analyses showed that miR-212-5p expression was increased with angiotensin II treatment in vivo and in vitro. Moreover, miR-212-5p mimic treatment attenuated and miR-212-5p inhibitor treatment increased VSMC proliferation and migration. Additionally, miR-212-5p mimic treatment suppressed VSMC contraction and related gene expression [Ras homolog gene family member A (RhoA) and Rho-associated protein kinase 2], while miR-212-5p inhibitor treatment exerted opposite effects. Bioinformatics analysis revealed that platelet-activating factor acetylhydrolase 1B2 (PAFAH1B2) is a target of miR-212-5p. miR-212-5p mimic treatment significantly reduced and miR-212-5p inhibitor treatment increased PAFAH1B2 expression. Furthermore, PAFAH1B2 expression was decreased in angiotensin II-treated aortic tissues and VSMCs. PAFAH1B2 was ubiquitously expressed in most adult rat tissues. In the vasculature, PAFAH1B2 was only distributed in the cytoplasm. PAFAH1B2 overexpression decreased A10 cell proliferation, while PAFAH1B2 knockdown increased A10 cell proliferation and cyclin D1 mRNA levels. PAFAH1B2 knockdown stimulated VSMC contraction and RhoA expression. These results suggest that miR-212-5p and PAFAH1B2 are novel negative regulators of VSMC proliferation, migration, and contraction in hypertension.

miR-135a-5p overexpression in peripheral blood-derived exosomes mediates vascular injury in type 2 diabetes patients

“…Previous studies have shown that the high expression of miR-212-5p can downregulate RhoA through its target PAFAH1B2 to inhibit vascular proliferation and contraction (29). Our study revealed a significant decrease in the expression level of hsa-miR-212-5p in exosomes from T2D patients.…”

Identified Small Open Reading Frame-Encoded Peptides in Human Serum with Nanoparticle Protein Coronas

“…The alpha2 catalytic subunit of the cytoplasmic platelet-activating factor I (PAF) acetylhydrolase (PAF-AH (I)) isotetramerase can catalyze the hydrolysis of the sn-2 acetyl group of PAF and regulate its activity . A study has pointed out that PAFAHB12, the downstream target of miR-212-5p, can suppress the proliferation of vascular smooth muscle cells and vascular contraction …”

“…46 A study has pointed out that PAFAHB12, the downstream target of miR-212-5p, can suppress the proliferation of vascular smooth muscle cells and vascular contraction. 47…”

Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-β1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis

“…miRNAs, a unique class of noncoding RNAs, can regulate their target genes at the transcriptional level, thereby participating in physiological activity and disease development. It has been widely reported that miR-212-5p plays different roles in various diseases, such as diabetes mellitus, colorectal cancer liver metastasis, and hypertension. − Even in fibrotic diseases, the functions of miR-212-5p are different. In cardiac fibrosis, miR-212-5p targets c-Myc and NLRC5, ultimately inhibiting the proliferation and activation of fibroblasts and collagen deposition. , In contrast, a study showed that miR-212-5p contributed to the progression of renal interstitial fibrosis by regulating a hypoxia-inducible factor 1-α inhibitor in the kidney tissues of UUO mice .…”