scholarly journals LncRNA MRAK048635_P1 is critical for vascular smooth muscle cell function and phenotypic switching in essential hypertension

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Genqiang Fang ◽  
Jia Qi ◽  
Liya Huang ◽  
Xianxian Zhao
Keyword(s):  
Smooth Muscle ◽  
Essential Hypertension ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Remodeling ◽  
Cell Function ◽  
Phenotypic Switching ◽  
And Migration ◽  
Proliferation And Migration

AbstractVascular remodeling caused by essential hypertension is a leading cause of death in patients, and vascular smooth muscle cell (VSMC) dysfunction and phenotypic switching result in vascular remodeling. Therefore, inhibiting cell dysfunction and phenotypic switching in VSMCs may be a new treatment strategy for essential hypertension. The aim of the current study is to explore the roles of long non-coding RNA (lncRNA) MRAK048635_P1 in VSMC function and phenotypic switching. The MRAK048635_P1 level was determined in spontaneously hypertensive rats (SHRs) and VSMCs isolated from SHRs. MRAK048635_P1 was knocked down using a specific siRNA in VSMCs isolated from the thoracic aorta of SHRs and Wistar–Kyoto rats. Then, the proliferation and migration of VSMCs were determined using a cell counting kit-8 (CCK-8), a 3H labeling method, a transwell assay, and a wound healing assay. Flow cytometry was used to test the effect of MRAK048635_P1 on VSMC apoptosis. The protein and mRNA levels of associated genes were measured through Western blotting, immunofluorescence, and Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). MRAK048635_P1 showed low expression during hypertension in vivo and in vitro. Down-regulation of lncRNA MRAK048635_P1 promoted proliferation and migration and inhibited apoptosis in VSMCs isolated from healthy rat vascular tissue and SHR-derived VSMCs. Importantly, we also found that down-regulation of MRAK048635_P1 could induce VSMC phenotypic switching from a contractile to a secretory phenotype. In conclusion, our findings reveal that decreased MRAK048635_P1 is probably an important factor for vascular remodeling by affecting VSMC cell function and phenotypic switching in essential hypertension.

miRNA 146b-5p protects against atherosclerosis by inhibiting vascular smooth muscle cell proliferation and migration

Epigenomics ◽  
2020 ◽  
Author(s):  
Dating Sun ◽  
Gui Xiang ◽  
Jing Wang ◽  
Yuanyuan Li ◽  
Shuai Mei ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Cell Function ◽  
Neointima Formation ◽  
And Migration ◽  
Aortic Plaques ◽  
Proliferation And Migration

Aim: To explore the potentially important role of miRNA 146b-5p (miR-146b) during the development of atherosclerosis. Materials & methods: Proliferation, migration and luciferase assays and mouse models were used to determine the functions of miR-146b. Results: miR-146b was identified as substantially upregulated in the aortic plaques of ApoE-/- mice as well as in response to inflammatory cytokines. Overexpression of miR-146b repressed proliferation and migration of vascular smooth muscle cells by downregulating Bag1 and Mmp16, respectively. Adeno-associated virus-mediated miR-146b overexpression inhibited neointima formation after carotid injury and suppressed atherosclerotic plaque formation in western diet-induced ApoE-/- mice. Conclusion: miR-146b is a novel regulator of vascular smooth muscle cell function induced by inflammatory response, specifically in neointima formation, and offers a novel therapeutic strategy for treating atherosclerosis.

scholarly journals Contribution of transcription factor EB to adipoRon-induced inhibition of arterial smooth muscle cell proliferation and migration

2019 ◽  
Vol 317 (5) ◽  
pp. C1034-C1047 ◽  
Author(s):  
Yun-Ting Wang ◽  
Jiajie Chen ◽  
Xiang Li ◽  
Michihisa Umetani ◽  
Yang Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Remodeling ◽  
Therapeutic Effects ◽  
Transcription Factor Eb ◽  
And Migration ◽  
Proliferation And Migration

Abnormal vascular smooth muscle cell (SMC) dedifferentiation with increased proliferation and migration during pathological vascular remodeling is associated with vascular disorders, such as atherosclerosis and in-stent restenosis. AdipoRon, a selective agonist of adiponectin receptor, has been shown to protect against vascular remodeling by preventing SMC dedifferentiation. However, the molecular mechanisms that mediate adipoRon-induced SMC differentiation are not well understood. The present study aimed to elucidate the role of transcription factor EB (TFEB), a master regulator of autophagy, in mediating adipoRon’s effect on SMCs. In cultured arterial SMCs, adipoRon dose-dependently increased TFEB activation, which is accompanied by upregulated transcription of genes involved in autophagy pathway and enhanced autophagic flux. In parallel, adipoRon suppressed serum-induced cell proliferation and caused cell cycle arrest. Moreover, adipoRon inhibited SMC migration as characterized by wound-healing retardation, F-actin reorganization, and matrix metalloproteinase-9 downregulation. These inhibitory effects of adipoRon on proliferation and migration were attenuated by TFEB gene silencing. Mechanistically, activation of TFEB by adipoRon is dependent on intracellular calcium, but it is not associated with changes in AMPK, ERK1/2, Akt, or molecular target of rapamycin complex 1 activation. Using ex vivo aortic explants, we demonstrated that adipoRon inhibited sprouts that had outgrown from aortic rings, whereas lentiviral TFEB shRNA transduction significantly reversed this effect of adipoRon on aortic rings. Taken together, our results indicate that adipoRon activates TFEB signaling that helps maintain the quiescent and differentiated status of arterial SMCs, preventing abnormal SMC dedifferentiation. This study provides novel mechanistic insights into understanding the therapeutic effects of adipoRon on TFEB signaling and pathological vascular remodeling.

Abstract 239: Olfactomedin 2 Regulates Vascular Smooth Muscle Cell Phenotypic Modulation by Mediating the Interaction Between Runx2 and SRF

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Ning Shi ◽  
Xiao-Bing Cui ◽  
Shi-You Chen
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Marker Genes ◽  
Important Process ◽  
Phenotypic Modulation ◽  
And Migration ◽  
Proliferation And Migration

Olfactomedin 2 (Olfm2) is a novel regulator for vascular smooth muscle cell (SMC) differentiation, but it is unclear whether Olfm2 is also involved in SMC phenotypic modulation, an important process associated with vascular injury. In this study, we found that Olfm2 was induced during PDGF-BB-induced SMC phenotypic modulation. Olfm2 knockdown attenuated PDGF-BB-induced suppression of SM marker genes including SM myosin heavy chain and SM22α, and also inhibited PDGF-BB-stimulated SMC proliferation and migration. On the other hand, Olfm2 overexpression down-regulated SM markers gene expression, and promoted SMC proliferation marker PCNA expression. Moreover, PDGF-BB slightly induced expression of Runx2, which interfered with the formation of SRF/myocardin ternary complex, but dramatically enhanced SRF-Runx2 interaction, suggesting that certain factors mediate SRF-Runx2 interaction. Indeed, Olfm2 physically interacted with both SRF and Runx2. Blockade of Olfm2 inhibited SRF association with Runx2, leading to increased association between SRF and myocardin, which in turn activated the transcription of SM markers, whereas overexpression of Olfm2 promoted SRF binding to Runx2. These results demonstrated that Olfm2 mediates the interaction between SRF and Runx2, contributing to SMC phenotypic modulation.

scholarly journals Long Non-Coding RNA MEG3 Downregulation Triggers Human Pulmonary Artery Smooth Muscle Cell Proliferation and Migration via the p53 Signaling Pathway

2017 ◽  
Vol 42 (6) ◽  
pp. 2569-2581 ◽  
Author(s):  
Zengxian Sun ◽  
Xiaowei Nie ◽  
Shuyang Sun ◽  
Shumin Dong ◽  
Chunluan Yuan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Remodeling ◽  
Pulmonary Artery Smooth Muscle ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Increasing evidence has demonstrated a significant role of long non-coding RNAs (lncRNAs) in diverse biological processes, and many of which are likely to have functional roles in vascular remodeling. However, their functions in pulmonary arterial hypertension (PAH) remain largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Pulmonary artery smooth muscle cells (PASMCs) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of PASMCs function. Herein, we determined whether long noncoding RNA–maternally expressed gene 3 (MEG3) was involved in PAH-related vascular remodeling. Methods: The arterial wall thickness was examined by hematoxylin and eosin (H&E) staining in distal pulmonary arteries (PAs) isolated from lungs of healthy volunteers and PAH patients. The expression level of MEG3 was analyzed by qPCR. The effects of MEG3 on human PASMCs were assessed by cell counting Kit-8 assay, BrdU incorporation assay, flow cytometry, scratch-wound assay, immunofluorescence, and western blotting in human PASMCs. Results: We revealed that the expression of MEG3 was significantly downregulated in lung and PAs of patients with PAH. MEG3 knockdown affected PASMCs proliferation and migration in vitro. Moreover, inhibition of MEG3 regulated the cell cycle progression and made more smooth muscle cells from the G0/G1 phase to the G2/M+S phase and the process could stimulate the expression of PCNA, Cyclin A and Cyclin E. In addition, we found that the p53 pathway was involved in MEG3–induced smooth muscle cell proliferation. Conclusions: This study identified MEG3 as a critical regulator in PAH and demonstrated the potential of gene therapy and drug development for treating PAH.

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