MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

Chen, Hanqing; Xu, Xiru; Zhengqing, Liu; Wu, Yong

doi:10.1159/000514311

Cited by 13 publications

(8 citation statements)

References 53 publications

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“…Similarly, Fu et al observed that miR-22-3p down-regulation facilitated the proliferative and migrating properties of VSMCs in atherosclerosis. 21) In addition, the research of Chen et al unraveled that miR-22-3p overexpression caused the transformation of aortic SMCs from the synthetic to contractile phenotype, 22) which was concurrent with our finding. Moreover, it was documented that the dysregulation of ECs is another mechanism implicated in ISR in addition to ECM deposition, aberrant proliferation, phenotype transformation, and migration of VSMCs.…”

Section: Discussionsupporting

confidence: 90%

MicroRNA-22-3p Restrains the Proliferation, Phenotypic Transformation, and Migration of Vascular Smooth Muscle Cells by Manipulating TOMM40

Tan

Yang

Bao³

et al. 2022

Int. Heart J.

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microRNA (miR)-22-3p has been confirmed to be engaged in the phenotype transformation and proliferation of vascular smooth muscle cells (VSMCs), which is intimately correlated with restenosis. The current research set out to explore the detailed mechanism and function of miR-22-3p in VSMC proliferation, phenotype transformation, and migration via the translocase of outer mitochondrial membrane (TOMM40). Peripheral blood samples were acquired from patients with in-stent restenosis (ISR) after percutaneous coronary intervention (PCI), with subsequent quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot analyses of miR-22-3p and TOMM40 expression. After miR-22-3p-inhibitor, oe-TOMM40, and sh-TOMM40 were transfected into VSMCs, Cell Counting Kit (CCK)-8 assay, scratch test, and Western blot analysis were implemented to measure the VSMC proliferation, migration, and matrix metallopeptidase 9 (MMP9), α-smooth muscle actin (SMA), smooth muscle-myosin heavy chain (SM-MHC), and osteopontin (OPN) expressions, respectively. In addition, human umbilical vein endothelial cell (HUVEC) proliferation was examined by CCK-8 assay. The binding relationship between miR-22-3p and TOMM40 was assessed by dual luciferase reporter and RNA immunoprecipitation assays. The peripheral blood of patients with ISR after PCI had low expression of miR-22-3p and high expression of TOMM40. The mechanistic analysis reported the negative targeting relationship between miR-22-3p and TOMM40. Down-regulating miR-22-3p or up-regulating TOMM40 elevated the proliferation, migration, and phenotype transformation of VSMCs. miR-22-3p inhibitor had no evident impact on HUVEC proliferation. In addition, rescue assays displayed that TOMM40 silencing annulled miR-22-3p inhibition-enhanced VSMC proliferation, migration, and phenotype transformation. Conclusively, miR-22-3p could repress VSMC proliferation, phenotypic transformation, and migration by targeting TOMM40, which might be a possible treatment candidate for restenosis after PCI in patients with cardiovascular disease.

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Section: Discussionsupporting

confidence: 90%

MicroRNA-22-3p Restrains the Proliferation, Phenotypic Transformation, and Migration of Vascular Smooth Muscle Cells by Manipulating TOMM40

Tan

Yang

Bao³

et al. 2022

Int. Heart J.

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“…These results indicated that holding miR‐22‐3p at the physiological level was required for maintaining oxidative balance. Interestingly, a previous study demonstrated that miR‐22‐3p was responsible for suppressing oxidative stress in aortic vascular cells of SHRs (Chen et al., 2021). The probable reason for these two conflicting results may be attributed to a downstream target difference.…”

Section: Discussionmentioning

confidence: 99%

miR‐22‐3p in the rostral ventrolateral medulla promotes hypertension through inhibiting β‐arrestin‐1

Wang,

Sun,

et al. 2023

The Journal of Physiology

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It has been documented that increased sympathetic activity contributes to the development of cardiovascular diseases, such as hypertension. We previously reported that β‐arrestin‐1, a multifunctional cytoskeletal protein, was downregulated in the rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rat (SHR), and its overexpression elicited an inhibitory effect on sympathetic activity in hypertension. microRNA (miR)‐22‐3p has been reported to be associated with the pathological progress of hypertension. The purpose of this study was to determine the role of miR‐22‐3p in β‐arrestin‐1‐mediated central cardiovascular regulation in hypertension. It was observed that miR‐22‐3p was upregulated in the RVLM of SHRs compared with normotensive Wistar–Kyoto (WKY) rats, and it was subsequently confirmed to target the β‐arrestin‐1 gene using a dual‐luciferase reporter assay. miR‐22‐3p was downregulated in the RVLM using adeno‐associated virus with ‘tough decoys’, which caused a significant increase of β‐arrestin‐1 expression and decrease of noradrenaline and blood pressure (BP) in SHRs. However, upregulation of miR‐22‐3p using lentivirus in the RVLM of WKY rats significantly increased BP. In in vitro PC12 cells, enhanced oxidative stress activity induced by angiotensin II was counteracted by pretreatment with miR‐22‐3p inhibitor, and this effect could be abolished by β‐arrestin‐1 gene knockdown. Furthermore, microglia exhaustion significantly diminished miR‐22‐3p expression, and enhanced β‐arrestin‐1 expression in the RVLM of SHRs. Activation of BV2 cells in vitro evoked a significant increase of miR‐22‐3p expression, and this BV2 cell culture medium was also able to facilitate miR‐22‐3p expression in PC12 cells. Collectively, our findings support a critical role for microglia‐derived miR‐22‐3p in inhibiting β‐arrestin‐1 in the RVLM, which is involved in central cardiovascular regulation in hypertension. imageKey points Impairment of β‐arrestin‐1 function in the rostral ventrolateral medulla (RVLM) has been reported to be associated with the development of sympathetic overactivity in hypertension. However, little is known about the potential mechanisms of β‐arrestin‐1 dysfunction in hypertension. miR‐22‐3p is implicated in multiple biological processes, but the role of miR‐22‐3p in central regulation of cardiovascular activity in hypertension remains unknown. We predicted that miR‐22‐3p could directly bind to the β‐arrestin‐1 gene (Arrb1), and this hypothesis was confirmed by using a dual‐luciferase reporter assay. Inhibition of β‐arrestin‐1 by miR‐22‐3p was further verified in both in vivo and in vitro experiments. Furthermore, our results suggested miR‐22‐3p as a risk factor for oxidative stress in the RVLM, thus contributing to sympatho‐excitation and hypertension. Our present study provides evidence that microglia‐derived miR‐22‐3p may underlie the pathogenesis and progression of neuronal hypertension by inhibiting β‐arrestin‐1 in the RVLM.

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“…A previous study found that LMNA (lamin A/C) [85], SLC11A2 [163], CRTC2 [164], TBK1 [165], GRN (granulin precursor) [166], CTSD (cathepsin D) [167], STARD10 [168], PGRMC1 [169], TFE3 [170], POR (cytochrome p450 oxidoreductase) [171], SESN1 [172], IL15 [173], PIK3R1 [134], OSM (oncostatin M) [98], SOCS3 [174], USP21 [100], GLUL (glutamate-ammonia ligase) [175], IL1R1 [176], TP53 [177], PPM1A [178], CTBP1 [179], DNAJC3 [180], ATP6 [181], DDX21 [182], COX2 [183], RACK1 [184], ND1 [158], CCND2 [185] and COX1 [186] are positively correlated with type 2 diabetes mellitus, suggesting its potential as a biomarker for type 2 diabetes mellitus. LMNA (lamin A/C) [187], PFKFB3 [188], TRAF2 [189], ADORA2B [190], ACADS (acyl-CoA dehydrogenase short chain) [191], IRF7 [192], ASL (argininosuccinatelyase) [193], IL15 [194], PIK3R1 [195], OSM (oncostatin M) [196], SOCS3 [197], CHD9 [198], IFI44L [199], GNLY (granulysin) [200], FLNB (filamin B) [201], IL1R1 [202], SETD3 [203], TP53 [204], BRD4 [205], COX2 [206], HSP90AB1 [207], SLC7A1 [208], ND2 [209] and COX1 [210] have been reported to be associated with hypertension. LMNA (lamin A/C) [211], INPP5K [212], SCYL1 [213], AKR7A2 [214], TRAF2 [215], SLC11A2 [216], NEU1 [217], SNAP29 [218], DUSP22 [219], P2RX4 [220], ADORA2B [221], NAXD (NAD(P)HX dehydratase) [222], FEZ1 [223], TBK1 [224], GRN (granulin precursor) [225], ATG4D [226], CTSD (cathepsin D) [227], PPP2R5D […”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

Vastrad¹,

Vastrad²

2022

Preprint

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Type 1 diabetes mellitus (T1DM) comprise the most common forms of autoimmune disease. The aim of this investigation was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of T1DM. The next generation sequencing (NGS) dataset GSE182870 was downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the differentially expressed genes. Protein-protein interaction (PPI) network, modules, miRNA-hub gene regulatory network, and TF-hub gene regulatory network were conducted via comprehensive target prediction and network analyses. Finally, hub genes were validated by using receiver operating characteristic curve analysis. A total of 860 DEGs were screened out from NGS dataset, among which 477 genes were up regulated and 383 genes were down regulated. GO enrichment analysis indicated that up regulated genes were mainly involved in cellular metabolic process, intracellular anatomical structure and catalytic activity, and the down regulated genes were significantly enriched in cellular nitrogen compound biosynthetic process, protein containing complex and heterocyclic compound binding. REACTOME pathway enrichment analysis showed that the up regulated genes were mainly enriched in metabolism of carbohydrates and the down regulated genes were significantly enriched in metabolism of RNA. A PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed, and hub genes (MAPK14, RHOC, MAD2L1, TAF1, TRAF2, HSP90AA1, TP53, HSP90AB1, UBA52 and RACK1) were identified. This study provides further insights into the underlying pathogenesis of T1DM.

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MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

Cited by 13 publications

References 53 publications

MicroRNA-22-3p Restrains the Proliferation, Phenotypic Transformation, and Migration of Vascular Smooth Muscle Cells by Manipulating TOMM40

MicroRNA-22-3p Restrains the Proliferation, Phenotypic Transformation, and Migration of Vascular Smooth Muscle Cells by Manipulating TOMM40

miR‐22‐3p in the rostral ventrolateral medulla promotes hypertension through inhibiting β‐arrestin‐1

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

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