CircSOD2: A Novel Regulator for Smooth Muscle Proliferation and Neointima Formation

2021 ◽  
Author(s):  
Xiaohan Mei ◽  
Xiao-Bing Cui ◽  
Yiran Li ◽  
Shi-You Chen
Keyword(s):  
Smooth Muscle ◽  
Vascular Injury ◽  
Noncoding Rna ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Circular Rna ◽  
In Vivo Studies ◽  
Circular Rnas ◽  
Neointima Formation ◽  
Specific Expression

Objective: Vascular smooth muscle cell (SMC) proliferation contributes to neointima formation following vascular injury. Circular RNA—a novel type of noncoding RNA with closed-loop structure—exhibits cell- and tissue-specific expression patterns. However, the role of circular RNA in SMC proliferation and neointima formation is largely unknown. The objective of this study is to investigate the role and mechanism of circSOD2 in SMC proliferation and neointima formation. Approach and Results: Circular RNA profiling of human aortic SMCs revealed that PDGF (platelet-derived growth factor)-BB up- and downregulated numerous circular RNAs. Among them, circSOD2, derived from back-splicing event of SOD2 (superoxide dismutase 2), was significantly enriched. Knockdown of circSOD2 by short hairpin RNA blocked PDGF-BB–induced SMC proliferation. Inversely, circSOD2 ectopic expression promoted SMC proliferation. Mechanistically, circSOD2 acted as a sponge for miR-206, leading to upregulation of NOTCH3 and NOTCH3 signaling, which regulates cyclin D1 and CDK (cyclin-dependent kinase) 4/6. In vivo studies showed that circSOD2 was induced in neointima SMCs in balloon-injured rat carotid arteries. Importantly, knockdown of circSOD2 attenuated injury-induced neointima formation along with decreased neointimal SMC proliferation. Conclusions: CircSOD2 is a novel regulator mediating SMC proliferation and neointima formation following vascular injury. Therefore, circSOD2 could be a potential therapeutic target for inhibiting the development of proliferative vascular diseases.

scholarly journals Transcriptomes Analysis Reveals the Regulatory Roles of Noncoding RNA in Tanshinones Synthesis Pathway of Salvia Miltiorrhiza

2021 ◽  
Author(s):  
Caicai Lin ◽  
Changhao Zhou ◽  
Zhongqian Liu ◽  
Xingfeng Li ◽  
Zhenqiao Song
Keyword(s):  
Noncoding Rna ◽  
Target Genes ◽  
Salvia Miltiorrhiza ◽  
Expression Patterns ◽  
Noncoding Rnas ◽  
Synthesis Process ◽  
Circular Rnas ◽  
Regulation Mechanism ◽  
Pentatricopeptide Repeat ◽  
Specific Expression

Abstract Background: Long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been shown to play fundamental roles in plant development. However, the information of these noncoding RNAs (ncRNAs) in Salvia miltiorrhiza remains largely unexplored. In this study, the expression pattern of ncRNAs in six tissues from the same strain of S. miltiorrhiza was analyzed to study the biological function of ncRNAs on active ingredients synthesis.Methods: Analysis of tanshinone content differences of two root simples was carried out on high-performance liquid chromatography (HPLC). RNA sequencing, GO and KEGG enrichment analysis were applied to analyzing the targets of diferentially expressed ncRNAs in different organs.Results: A total of 6,929 lncRNAs, 6,239 circRNAs, and 360 miRNAs were identified. Forty-eight lncRNAs, 70 miRNAs, and 26 circRNAs expressed differentially between red and white root tissues with significantly different tanshinone content. GO and KEGG pathway analysis of target genes of differently expressed ncRNAs indicated that some target genes are involved in the synthesis pathway of terpene, including diterpene and sesquiterpene. We also found many target genes related to secondary metabolites, including 2-C-Methyl-d-erythritol 2,4-cyclodiphosphate Synthase (SmMCS) and several CYP450s. Furthermore, most target genes may be related to the resistance of pathogens, such as receptor kinases, disease-resistant proteins, and pentatricopeptide repeat-containing proteins. Conclusions: The present study exhibited the tissue-specific expression patterns of ncRNAs preliminarily in S. miltiorrhiza, which may reflect that the formation of white root or red root is related to regulation by ncRNAs. It would provide a basis for further research about the regulation mechanism in the tanshinone synthesis process.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Abstract 5494: ADAMTS-7 is Critical for Vascular Smooth Muscle Cell Migration and Neointima Formation in Injured Rat Carotid Artery

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Wei Kong ◽  
Li Wang ◽  
Xue Bai ◽  
Bo Liu ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Injury ◽  
Matrix Protein ◽  
Mrna Level ◽  
Balloon Catheter ◽  
Migration And Invasion ◽  
Neointima Formation ◽  
Subsequent Increase ◽  
Neointimal Thickening

Migration of vascular smooth muscle cells (VSMCs) plays an essential role during vascular development, in response to vascular injury and during atherogenesis. Extensive studies have implicated the importance of extracellular matrix (ECM)-degrading proteinases during VSMCs migration. ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), a recently described family of proteinases, is capable of degrading vascular ECM proteins. However, the relevance of ADAMTS family members in cardiovascular disease is poorly understood. In this study, we sought to determine whether ADAMTS-7 is involved in VSMC migration and neointima formation in response to vascular injury. Denudation of rat carotid arteries with a balloon catheter led to an initial decrease of ADAMTS-7 protein level in injured compared with sham-operated arteries within the first 24 hours, followed by a subsequent increase during the 4 to 14 days after injury. In primary VSMCs, the pro-inflammatory cytokine TNF-α increased ADAMTS-7 mRNA level through transcriptional factors nuclear factor-kappa B and AP-1. VSMCs infected with ADAMTS-7 adenovirus (Ad-ADAMTS-7) greatly accelerated their migration and invasion in vitro . Conversely, suppression of ADAMTS-7 expression by small interfering RNA (siRNA) markedly retarded VSMC movement by 50% than that with scramble siRNA. At 7 days after injury, the neointimal area of the vascular wall was sixfold greater in Ad-ADAMTS-7-infected than that in Ad-GFP-infected vessels (3.10±0.88 vs. 0.52±0.28 ×10 4 μm 2 , n=8 per group, P <0.05). By contrast, perivascular administration of ADAMTS-7 siRNA, but not scramble siRNA to injured arteries resulted in prolonged ADAMTS-7 silencing and diminished neointimal thickening without affecting medial areas. This inhibitory effect was sustained up to 14 days after injury. As well, ADAMTS-7 mediated degradation of the vascular ECM cartilage oligomeric matrix protein (COMP) in injured vessels, which might facilitate VSMC migration and neointimal thickening. ADAMTS-7 directs VSMC migration and neointima formation and therefore may serve as a novel therapeutic target for vascular restenosis and atherogenesis.

scholarly journals Age-Dependent and -Independent Effects of Perivascular Adipose Tissue and Its Paracrine Activities during Neointima Formation

2019 ◽  
Vol 21 (1) ◽  
pp. 282 ◽  
Author(s):  
Eva Schütz ◽  
Rajinikanth Gogiraju ◽  
Maria Pavlaki ◽  
Ioannis Drosos ◽  
George S. Georgiadis ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Smooth Muscle ◽  
Vascular Injury ◽  
Pcr Analysis ◽  
Aortic Tissue ◽  
Neointima Formation ◽  
Middle Aged ◽  
Perivascular Adipose Tissue ◽  
Independent Effects ◽  
And Function

Cardiovascular risk factors may act by modulating the composition and function of the adventitia. Here we examine how age affects perivascular adipose tissue (PVAT) and its paracrine activities during neointima formation. Aortic tissue and PVAT or primary aortic smooth muscle cells from male C57BL/6JRj mice aged 52 weeks (“middle-aged”) were compared to tissue or cells from mice aged 16 weeks (“adult”). Vascular injury was induced at the carotid artery using 10% ferric chloride. Carotid arteries from the middle-aged mice exhibited smooth muscle de-differentiation and elevated senescence marker expression, and vascular injury further aggravated media and adventitia thickening. Perivascular transplantation of PVAT had no effect on these parameters, but age-independently reduced neointima formation and lumen stenosis. Quantitative PCR analysis revealed a blunted increase in senescence-associated proinflammatory changes in perivascular tissue compared to visceral adipose tissue and higher expression of mediators attenuating neointima formation. Elevated levels of protein inhibitor of activated STAT1 (PIAS1) and lower expression of STAT1- or NFκB-regulated genes involved in adipocyte differentiation, inflammation, and apoptosis/senescence were present in mouse PVAT, whereas PIAS1 was reduced in the PVAT of patients with atherosclerotic vessel disease. Our findings suggest that age affects adipose tissue and its paracrine vascular activities in a depot-specific manner. PIAS1 may mediate the age-independent vasculoprotective effects of perivascular fat.

scholarly journals Inhibition of Smooth Muscle β-Catenin Hinders Neointima Formation After Vascular Injury

2017 ◽  
Vol 37 (5) ◽  
pp. 879-888 ◽  
Author(s):  
Dario F. Riascos-Bernal ◽  
Prameladevi Chinnasamy ◽  
Jordana N. Gross ◽  
Vanessa Almonte ◽  
Lander Egaña-Gorroño ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Injury ◽  
Neointima Formation

KVα1 channels in murine arterioles: differential cellular expression and regulation of diameter

2001 ◽  
Vol 281 (3) ◽  
pp. H1057-H1065 ◽  
Author(s):  
A. Cheong ◽  
A. M. Dedman ◽  
S. Z. Xu ◽  
D. J. Beech
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Expression Profiles ◽  
Second Messengers ◽  
Expression Patterns ◽  
Muscle Cells ◽  
Cell Types ◽  
Specific Expression ◽  
Major Function ◽  
Cellular Expression

The primary objectives of this study were to reveal cell-specific expression patterns and functions of voltage-gated K+ channel (KVα1) subunits in precapillary arterioles of the murine cerebral circulation. KVα1 were detected using peptide-specific antibodies in immunofluorescence and Western blotting assays. KV1.2 was localized almost exclusively to endothelial cells, whereas KV1.5 was discretely localized to the nerves and nerve terminals that innervate the arterioles. KV1.5 also localized specifically to arteriolar nerves in human pial membrane. KV1.5 was notable for its absence from smooth muscle cells. KV1.3, KV1.4, and KV1.6 were localized to endothelial and smooth muscle cells, although KV1.4 had a low expression level. KV1.1 was not expressed. Therefore, we show that different cell types of pial arterioles have distinct physiological expression profiles of KVα1, conferring the possibility of differential modulation by extracellular and second messengers. Furthermore, we show recombinant agitoxin-2 and margatoxin are potent vasoconstrictors, suggesting that KVα1 subunits have a major function in determining arteriolar resistance to blood flow.

scholarly journals Systematic Analysis of Gibberellin Pathway Components in Medicago truncatula Reveals the Potential Application of Gibberellin in Biomass Improvement

2020 ◽  
Vol 21 (19) ◽  
pp. 7180
Author(s):  
Hongfeng Wang ◽  
Hongjiao Jiang ◽  
Yiteng Xu ◽  
Yan Wang ◽  
Lin Zhu ◽  
...  
Keyword(s):  
Medicago Truncatula ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Feedback Regulation ◽  
Specific Expression ◽  
Systematic Analysis ◽  
Model Legume ◽  
Genome Wide ◽  
A Genome

Gibberellins (GAs), a class of phytohormones, act as an essential natural regulator of plant growth and development. Many studies have shown that GA is related to rhizobial infection and nodule organogenesis in legume species. However, thus far, GA metabolism and signaling components are largely unknown in the model legume Medicago truncatula. In this study, a genome-wide analysis of GA metabolism and signaling genes was carried out. In total 29 components, including 8 MtGA20ox genes, 2 MtGA3ox genes, 13 MtGA2ox genes, 3 MtGID1 genes, and 3 MtDELLA genes were identified in M. truncatula genome. Expression profiles revealed that most members of MtGAox, MtGID1, and MtDELLA showed tissue-specific expression patterns. In addition, the GA biosynthesis and deactivation genes displayed a feedback regulation on GA treatment, respectively. Yeast two-hybrid assays showed that all the three MtGID1s interacted with MtDELLA1 and MtDELLA2, suggesting that the MtGID1s are functional GA receptors. More importantly, M. truncatula exhibited increased plant height and biomass by ectopic expression of the MtGA20ox1, suggesting that enhanced GA response has the potential for forage improvement.

Circular RNAs as biomarkers in liquid biopsy in colorectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 230-230
Author(s):  
Manuel Valladares-Ayerbes ◽  
Carmen Garrigos ◽  
Miquel Taron ◽  
Angélica Figueroa ◽  
Enrique Aranda
Keyword(s):  
Colorectal Cancer ◽  
Bone Marrow ◽  
Expression Pattern ◽  
Liquid Biopsy ◽  
Expression Patterns ◽  
Target Prediction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Blood Leukocytes ◽  
Specific Expression

230 Background: Circular RNAs (circRNAs) are emerging as essential regulators of cancer- related biological hallmarks, as cell proliferation, apoptosis, differentiation, immune regulation and angiogenesis. CircRNAs are abundant, conserved, and have a tissue‐specific expression pattern. These characteristics make them candidate to serve as biomarkers in liquid biopsy (LB) in cancer. The aim of this study is to analyse differential expression of circRNAs in the colorectal cancer (CRC) scenario. Methods: To comprehensively understand the expression patterns of circRNAs we characterized 13,617 circRNAs using a microarray [Arraystar v2 (8x15K)] in 10 human samples, five CRC cell lines, one colorectal human tumour, one normal colon healthy control, vs. Peripheral Human Blood Leukocytes (2 pools) and Human Bone Marrow. Differentially expressed circRNAs were identified using fold change (FC) cut-off or through Volcano Plot filtering respectively. CircRNAs having FC ▪2 and P-values ▪ 0.05 were selected. CircRNA/microRNA interaction was predicted with target prediction software. Results: Hierarchical clustering showed distinguishable circRNA expression profiling among 10 samples. These data indicated that circRNAs have a different expression pattern in colorectal tissues compared with that in blood and bone marrow tissues. The microarray data showed 2329 circRNAs differentially expressed (FC > 2.0, P < 0.05). Among them, 964 circRNAs were upregulated and 1365 were downregulated in colon tissues compared with blood and bone marrow. Using a stringent criterion (FC > 10, P≤ 0.01 and false discovery rate [FDR] < 0.05) we have identified 30 circRNA upregulated in colorectal cancer versus non tumour samples. CircRNA/microRNA interaction prediction analysis showed that most upregulated circRNAs contain miRNA Binding Sites (MREs) for cancer-related miRNA, including among others, miR-17, miR-103, miR-let-7g. Conclusions: Microarray analysis was used to comprehensively identify dysregulated circRNAs in CRC. We identify novel circRNAs could be valuable as blood-based CRC biomarkers.

Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats

2005 ◽  
Vol 289 (3) ◽  
pp. H1047-H1053 ◽  
Author(s):  
D. K. Jagadeesha ◽  
Timothy E. Lindley ◽  
Jason DeLeon ◽  
Ram V. Sharma ◽  
Francis Miller ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Injury ◽  
Critical Role ◽  
Balloon Catheter ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Neointima Formation ◽  
Muscle Cell Apoptosis

Accumulating data support the hypothesis that reactive oxygen species (ROS) play a critical role in the vascular complications observed in diabetes. However, the mechanisms of ROS-mediated vascular complications in diabetes are not clear. We tested the hypothesis that ROS-mediated increase in proapoptotic factor Bax expression leads to medial smooth muscle cell (SMC) apoptosis that is associated with neointima formation. We used a fructose-rich diet for 4 wk to model Type 2 diabetes in rats. SOD mimetic membrane-permeable 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempol, 1 mM) was administered in drinking water to scavenge superoxide starting 1 day before surgery and continued during the duration of the experiment. Vascular injury resulted in a significant increase in medial SMC apoptosis that was associated with neointima formation. The number of medial SMC positive for Bax immunostaining significantly increased in injured arteries compared with uninjured arteries. Superoxide scavenging by Tempol treatment inhibited both the Bax-positive index as well as the apoptotic index of medial SMC in response to vascular injury. Tempol treatment inhibited apoptotic loss of medial SMC, thus increasing their density in the injured arteries. These alterations in the media were associated with a marked decrease in neointima formation in injured arteries. We conclude that Bax expression may play an important role in vascular SMC apoptosis and, finally, that this regulatory mechanism is redox sensitive.

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