MicroRNA‑153 attenuates hypoxia‑induced excessive proliferation and migration of pulmonary arterial smooth muscle cells by targeting ROCK1 and NFATc3

Zhao, Minjie; Wang, Wei; Lu, Ya; Wang, Nan; Kong, Delei; Shan, Lina

doi:10.3892/mmr.2021.11833

Cited by 17 publications

(3 citation statements)

References 50 publications

(45 reference statements)

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“…3a). Hypoxia increased Cd146, Rgs4, Rgs5, Nox4 , and Rock1 expression in smooth muscle cells [37-40], with Wt and Notch3 -Null cells exhibiting similar profiles (Fig. 3a) [37, 41-43].…”

Section: Resultsmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature

et al. 2022

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Pulmonary arterial hypertension (PAH) is a chronic progressive disease with significant morbidity and mortality. The disease is characterized by vascular remodeling that includes increased muscularization of distal blood vessels and vessel stiffening associated with changes in extracellular matrix deposition. In humans, chronic hypoxia causes PAH, and hypoxia-induced rodent models of PAH have been used for years to study the disease. With the development of single-cell RNA sequencing technology, it is now possible to examine hypoxia-dependent transcriptional changes in vivo at a cell-specific level. In this study, we used single-cell RNA sequencing to compare lungs from wild-type (Wt) mice exposed to hypoxia for 28 days to normoxia-treated control mice. We additionally examined mice deficient for <i>Notch3</i>, a smooth muscle-enriched gene linked to PAH. Data analysis revealed that hypoxia promoted cell number changes in immune and endothelial cell types in the lung, activated the innate immunity pathway, and resulted in specific changes in gene expression in vascular cells. Surprisingly, we found limited differences in lungs from mice deficient for <i>Notch3</i> compared to Wt controls. These findings provide novel insight into the effects of chronic hypoxia exposure on gene expression and cell phenotypes in vivo and identify unique changes to cells of the vasculature.

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“…3a). Hypoxia increased Cd146, Rgs4, Rgs5, Nox4 , and Rock1 expression in smooth muscle cells [37-40], with Wt and Notch3 -Null cells exhibiting similar profiles (Fig. 3a) [37, 41-43].…”

Section: Resultsmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature

et al. 2022

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“…The levels of miR-34a-5p, associated with atherosclerosis and miR-34a-5p, play a crucial role in inflammatory pathology [ 67 ] and various studies [ 68 , 69 ] have discussed miR-34a-5p, which was found to be inhibited in this study, as a potential therapeutic target in cardiovascular disease. miR-205-5p, which was found to be activated in this study, suppresses the proliferation of pulmonary VSMCs [ 70 ], whereas miR-153, which was found to be inhibited in this study, attenuates hypoxia-induced excessive proliferation and migration of pulmonary arterial SMCs [ 71 ]. miR-22, which was found to be inhibited in this study, regulates VSMCs apoptosis (through p38MAPKα) and vascular remodeling in aortic dissection [ 72 ], whereas miR-219, which was found to be inhibited in this study, is associated with vascular ischemia during cerebral artery occlusion [ 73 ] ( Table 1 and Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula

Rai

Agrawal

2022

Proteomes

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Arteriovenous fistulas (AVFs), created for hemodialysis in end-stage renal disease patients, mature through the outward remodeling of the outflow vein. However, early thrombosis and chronic inflammation are detrimental to the process of AVF maturation and precipitate AVF maturation failure. For the successful remodeling of the outflow vein, blood flow through the fistula is essential, but early arterial thrombosis attenuates this blood flow, and the vessels become thrombosed and stenosed, leading to AVF failure. The altered expression of various proteins involved in maintaining vessel patency or thrombosis is regulated by genes of which the expression is regulated by transcription factors and microRNAs. In this study, using thrombosed and stenosed arteries following AVF creation, we delineated transcription factors and microRNAs associated with differentially expressed genes in bulk RNA sequencing data using upstream and causal network analysis. We observed changes in many transcription factors and microRNAs that are involved in angiogenesis; vascular smooth muscle cell proliferation, migration, and phenotypic changes; endothelial cell function; hypoxia; oxidative stress; vessel remodeling; immune responses; and inflammation. These factors and microRNAs play a critical role in the underlying molecular mechanisms in AVF maturation. We also observed epigenetic factors involved in gene regulation associated with these molecular mechanisms. The results of this study indicate the importance of investigating the transcriptional and epigenetic regulation of AVF maturation and maturation failure and targeting factors precipitating early thrombosis and stenosis.

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“…COPD occurrence is also associated with aberrant miRNA expression (14). A former study reported that miR-153-3p repressed hypoxia-caused PASMC proliferation and migration in a pulmonary arterial hypertension (PAH) cell model (15). Moreover, miR-153-3p interacted with transforming growth factor beta receptor 2 to act an anti-fibrotic effect in pulmonary fibrosis (16).…”

Section: Introductionmentioning

confidence: 99%

Circ_0026466 Knockdown Protects Human Bronchial Epithelial Cells From Cigarette Smoke Extract–induced Injury by Promoting the Mir-153-3p/Traf6/Nf-Κb Pathway

Wang

Tang

Hou

et al. 2023

Shock

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Background: Considerable data have shown that circular RNAs (circRNAs) mediate the pathogenesis of chronic obstructive pulmonary disease (COPD). The study aims to analyze the function and mechanism of circ_0026466 in COPD. Methods: Human bronchial epithelial cells (16HBE) were treated with cigarette smoke extract (CSE) to establish a COPD cell model. Quantitative real-time polymerase chain reaction and Western blot were used to detect the expression of circ_0026466, microRNA-153-3p (miR-153-3p), TNF receptor associated factor 6 (TRAF6), cell apoptosis-related proteins, and NF-κB pathway-related proteins. Cell viability, proliferation, apoptosis, and inflammation were investigated by cell counting kit-8, EdU assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Oxidative stress was evaluated by lipid peroxidation malondialdehyde assay kit and superoxide dismutase activity assay kit. The interaction between miR-153-3p and circ_0026466 or TRAF6 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results: Circ_0026466 and TRAF6 expression were significantly increased, but miR-153-3p was decreased in the blood samples of smokers with COPD and CSE-induced 16HBE cells when compared with controls. CSE treatment inhibited the viability and proliferation of 16HBE cells but induced cell apoptosis, inflammation, and oxidative stress, but these effects were attenuated after circ_0026466 knockdown. Circ_0026466 interacted with miR-153-3p and regulated CSE-caused 16HBE cell damage by targeting miR-153-3p. Additionally, TRAF6, a target gene of miR-153-3p, regulated CSE-induced 16HBE cell injury by combining with miR-153-3p. Importantly, circ_0026466 activated NF-κB pathway by targeting the miR-153-3p/TRAF6 axis. Conclusion: Circ_0026466 absence protected against CSE-triggered 16HBE cell injury by activating the miR-153-3p/TRAF6/NF-κB pathway, providing a potential therapeutic target for COPD.

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MicroRNA‑153 attenuates hypoxia‑induced excessive proliferation and migration of pulmonary arterial smooth muscle cells by targeting ROCK1 and NFATc3

Cited by 17 publications

References 50 publications

Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature

Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature

Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula

Circ_0026466 Knockdown Protects Human Bronchial Epithelial Cells From Cigarette Smoke Extract–induced Injury by Promoting the Mir-153-3p/Traf6/Nf-Κb Pathway

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