Sp1, acetylated histone-3 and p300 regulate TRAIL transcription: Mechanisms of PDGF-BB-mediated VSMC proliferation and migration

2012 ◽  
Vol 113 (8) ◽  
pp. 2597-2606 ◽  
Author(s):  
Nor Saadah M. Azahri ◽  
Belinda A. Di Bartolo ◽  
Levon M. Khachigian ◽  
Mary M. Kavurma
Keyword(s):  
Vsmc Proliferation ◽  
Histone 3 ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Heyun Zhang ◽  
Zhangyu Zheng ◽  
Rongqin Zhang ◽  
Yongcong Yan ◽  
Yaorong Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Histone Methylation ◽  
Cell Growth And Migration ◽  
Histone 3 ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Proliferation And Migration

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.

Abstract 497: 5-Methoxytryptophan Protects Against Vascular Remodeling

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yen-Chun Ho ◽  
Meng-Ling Wu ◽  
Chen-Hsuan Su ◽  
Cheng-Chin Kuo ◽  
Kenneth K Wu ◽  
...  
Keyword(s):  
Vascular Disease ◽  
P38 Mapk ◽  
Vessel Wall ◽  
Neointima Formation ◽  
Phenotypic Modulation ◽  
Mapk Activation ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Vascular smooth muscle cells (VSMCs) in the blood vessel wall exhibit a differentiated phenotype; their main function is contraction and to regulate vascular tone. In response to injury, VSMCs undergo a phenotypic transition whereby they proliferate and migrate from the medial layer into the intima, contributing to lesion formation and atherosclerosis. 5-methoxytryptophan (5-MTP), a recently identified novel tryptophan metabolite, has been shown to inhibit cancer cell growth, migration, and cancer metastasis. We hypothesized that 5-MTP might play an analogous role in vascular disease as in tumorigenesis. To test our hypothesis, we subjected 12 weeks old C57BL/6 mice to a carotid artery cessation of blood flow model to induce neointima formation. Following surgery, mice were treated with vehicle (PBS) or 100 mg/kg of 5-MTP by intraperitoneal injection 3 times a week. Four weeks later, carotid arteries were harvested for histological analysis. H&E and elastin staining revealed robust neointima in ligated carotids of vehicle-treated mice. In contrast, 5-MTP significantly attenuated neointima formation. Given that proinflammatory cytokine interleukin 1 beta (IL-1β) is increased in the injured vessel wall, we examined whether IL-1β affected VSMC phenotypic modulation. Indeed, IL-1β downregulated VSMC marker SM α-actin expression and increased VSMC proliferation and migration. Importantly, in VSMCs, 5-MTP attenuated IL-1β-mediated SM α-actin downregulation, proliferation, and migration, suggesting a potential role of 5-MTP in controlling VSMC phenotypic modulation. Furthermore, 5-MTP inhibited IL-1β-mediated p38 MAPK activation. Inhibiting p38 MAPK activation by SB203580 dose-dependently decreased IL-1β-induced VSMC proliferation. Taken together, our results suggest an important role of 5-MTP in vascular disease.

Abstract 417: Adenosine Diphosphate Ribosyl Cyclase via PI3K-Akt and FOXO3a Up-regulating MMP-9 to Enhance Vascular Smooth Muscle Cell Proliferation and Migration in Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Yuming Li ◽  
Haitao Li ◽  
Xinfang Wang ◽  
Junya Wang ◽  
Zhongqiu Li
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Adenosine Diphosphate ◽  
High Fat ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

The current study was designed to explore the mechanisms of vascular smooth muscle cell (VSMC) proliferation and migration induced by adenosine diphosphate ribosyl cyclase(ADPRC). In this study, 32 Male ApoE-/- mice(6 weeks old, 18-22g)on a C57BL/6J background were divided into four groups, which received normal chow (n=8, NC group), high-fat Western-type diet (n=8, 0.25% cholesterol, 21% fat,HFD group), high-fat Western-type diet,infusion of 2,2′-dihydroxyazobenzene(DHAB, a ADPRC inhibitor, 2mg/kg/day, n=8, HFD-DHAB group) intraperitoneally or high-fat Western-type diet,infusion of LY294002(a Inhibitor of Akt, 5mg/kg/d, n=8, HFD-LY group) intraperitoneally, for 10 weeks. 8 male C57BL/6J mice served as control. After 10 weeks, mice were anesthetized with chloral hydrate, aorta was removed and immediately frozen in liquid nitrogen. Aortic atherosclerotic lesions, VSMC proliferation and migration were assessed by histomorphological observation, smooth muscle actin-α(α-SMA)and proliferating cell nuclear antigen (PCNA) examination. ADPRC expression and alterations of Akt, FOXO3a, phospho-FOXO3a and MMP-9 were determined by RT-PCR, Western Blot, Immunohistochemistry or Immunofluorescence. The results showed that, in aortic atherosclerotic lesions derived from atherosclerotic mice of HFD group, an increased VSMC proliferation and migration, reflected by the up-regulation of α-SMA and PCNA expression, were observed followed by increased expression of ADPRC, Akt, FOXO3a, phospho-FOXO3a and MMP-9. The enhanced expression of ADPRC and followed alterations of FOXO3a, phospho-FOXO3a, MMP-9 as well as α-SMA, PCNA, VSMC proliferation and migration were absent in NC group and C57BL/6J control mice. Treatment with DHAB or LY294002 reversed VSMC proliferation, migration and expression of Akt, FOXO3a, phospho-FOXO3a and MMP-9 in HFD-DHAB and HFD-LY group. These data shows that high-fat Western-type diet induced ADPRC may via PI3K-Akt to phosphorylate FOXO3a up-regulating MMP-9 to enhance vascular smooth muscle cell proliferation and migration in mice.

scholarly journals Avβ3 Single-Stranded DNA Aptamer Attenuates Vascular Smooth Muscle Cell Proliferation and Migration via Ras-PI3K/MAPK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Hong-Bing Wu ◽  
Zhi-Wei Wang ◽  
Feng Shi ◽  
Zong-Li Ren ◽  
Luo-Cheng Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cell Cycle Progression ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Dna Aptamer ◽  
Mitogen Activated Protein Kinase ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Objectives. To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. Background. Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs. Methods. In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot. Results. In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (P<0.05). Avβ3 ssDNA also inhibited VSMC proliferation and migration while promoting apoptosis (P<0.05), as demonstrated by the upregulation of the proapoptotic proteins Bax and active caspase 3 (P<0.05). Conclusions. The findings suggest that avβ3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.

TMEM98, a novel secretory protein, promotes endothelial cell adhesion as well as vascular smooth muscle cell proliferation and migration

2020 ◽  
Author(s):  
Mei Li ◽  
Hongmei Zhu ◽  
Xiaoyan Hu ◽  
Fuhua Gao ◽  
Xinxin Hu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Endothelial Cell ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Transmembrane Protein ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Transmembrane protein 98 (TMEM98) is a novel gene. In a prior study, we have shown that siRNA-mediated knockdown of TMEM98 inhibited interleukin (IL)-8-promoted endothelial cell (EC) adhesion as well as vascular smooth muscle cell (VSMC) proliferation and migration in the vascular endothelial and smooth muscle cells dysfunction. Herein, we used gain- and loss-of-function approaches combined with biochemical techniques to further explore the role of TMEM98 in the vascular wall cell. The expression and secretion of TMEM98 was increased in cultured human umbilical vein endothelial cells (HUVECs) and VSMCs treated with IL-8 and platelet-derived growth factor (PDGF)-BB. Also, PDGF-BB secretion was increased in TMEM98-treated HUVECs and VSMCs. Thus, it appears that TMEM98 and PDGF-BB form a positive feedback loop in potentiation of EC adhesion as well as VSMC proliferation and migration. Knockdown of TMEM98 mediated by siRNA inhibited PDGF-BB-promoted EC adhesion by downregulating the expression of ICAM-1 and VCAM-1 as well as impaired the proliferation and migration of VSMCs through suppressing the AKT/GSK3β/cyclin D1 signaling pathway and reducing the expression of β-catenin. Hence, TMEM98 promoted EC adhesion through inducing the expression of ICAM-1/VCAM-1 and triggered VSMC proliferation and migration through activating the ERK and AKT/GSK3β signaling pathways. Taken together, TMEM98 may serve as a potential therapeutic target for the clinical treatment.

scholarly journals MiR-9 promotes the phenotypic switch of vascular smooth muscle cells by targeting KLF5

2019 ◽  
Author(s):  
XIAOCHUN LU ◽  
SHITANG MA ◽  
BO ZHOU ◽  
TIELING LI
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Muscle Cells ◽  
Phenotypic Switch ◽  
Vsmc Proliferation ◽  
Qrt Pcr ◽  
And Migration ◽  
Proliferation And Migration

Background: Diabetic vascular smooth muscle cells (VSMCs) are characterized by increased proliferation and migration. Small non-coding microRNAs (miRNAs) have been considered critical modulators of VSMC phenotypic switch after an environmental stimulus. However, microRNA in high glucose-induced pro-inflammation and its atherogenic effect is still ambiguous. Methods: qRT-PCR was used to examine the expression of miR-9 in VSMCs. The downstream signaling protein relative to miR-9 regulation, Krüppel-like factor 5, and some marker genes of contractile VSMCs, were analyzed by western blotting and qRT-PCR. Luciferase reporter assay was used to detect the expression of KLF5, which is regulated by miR-9. To examine the function of a miR-9 inhibitor in VSMC proliferation and migration, VSMC proliferation and migration assays were performed. Results: Reduced transcriptional levels of miR-9 and expression of specific genes of contractile VSMCs were observed in the SMC cell line C-12511 treated with high glucose and SMCs, which were isolated from db/db mice. Moreover, the activity of KLF5 3′-UTR was dramatically reduced by a miR-9 mimic, and increased by a miR-9 inhibitor. The proliferation and migration of SMCs was reduced by the miR-9 mimic. Conclusion: miR-9 inhibits the proliferation and migration of SMC by targeting KLF5 in db/db mice. Keywords: miR-9; Smooth muscle cells; Proliferation; Migration; KLF5

scholarly journals Corylin Inhibits Vascular Cell Inflammation, Proliferation and Migration and Reduces Atherosclerosis in ApoE-Deficient Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 275
Author(s):  
Chin-Chuan Chen ◽  
Hung-Yuan Li ◽  
Yann-Lii Leu ◽  
Yu-Ju Chen ◽  
Chia-Jen Wang ◽  
...  
Keyword(s):  
Flavonoid Compound ◽  
Ros Production ◽  
Monocyte Adhesion ◽  
Vascular Cell ◽  
Vsmc Proliferation ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
And Migration ◽  
Deficient Mice ◽  
Proliferation And Migration

Atherosclerosis is a complex disease that includes several events, including reactive oxygen species (ROS) stress, inflammation, endothelial dysfunction, lipid deposition, and vascular smooth muscle cell (VSMC) proliferation and migration, which result in atherosclerotic plaque formation. Corylin, a flavonoid compound, is known to exhibit antioxidative, anti-inflammatory and antiproliferative effects. However, it remains unknown whether corylin could modulate atherogenesis. Here, we identified the anti-inflammatory effect of corylin in tumor necrosis factor-α (TNF-α)-induced vascular cells. In human umbilical vein endothelial cells (HUVECs), corylin suppressed TNF-α-induced monocyte adhesion to the HUVECs and transmigration by downregulating the ROS/JNK/nuclear factor-kappa beta (NF-κB) p65 pathway. In VSMCs, corylin inhibited TNF-α-induced monocyte adhesion by suppressing ROS production, mitogen-activated protein kinase (MAPK) phosphorylation and NF-κB p65 translocation. In platelet-derived growth factor-BB (PDGF-BB)-induced VSMCs, corylin inhibited PDGF-BB-induced VSMC proliferation and migration through regulating the mammalian target of rapamycin (mTOR)/dynamin-1-like protein 1 (Drp1) signaling cascade. In addition, corylin treatment not only attenuated atherosclerotic lesions, ROS production, vascular cell adhesion protein-1 (VCAM-1) expression, monocyte adhesion and VSMC proliferation in apolipoprotein E (ApoE)-deficient mice but also inhibited neointimal hyperplasia in endothelial-denuded mice. Thus, corylin may be a potential prevention and treatment for atherosclerosis.

scholarly journals Identification of a Novel Gene Correlated With Vascular Smooth Muscle Cells Proliferation and Migration in Chronic Thromboembolic Pulmonary Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Wang ◽  
Congrui Sun ◽  
Xiaoshuo Lv ◽  
Mingsheng Sun ◽  
Chaozeng Si ◽  
...  
Keyword(s):  
Vascular Remodeling ◽  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Vsmc Proliferation ◽  
Kegg Pathway Analysis ◽  
Tnf Α ◽  
Thromboembolic Pulmonary Hypertension ◽  
And Migration ◽  
Proliferation And Migration

Objective: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombofibrotic obstruction of the proximal pulmonary arteries, which result in vascular remodeling of the distal pulmonary artery. While the cellular and molecular mechanisms underlying CTEPH pathogenesis remain incompletely understood, recent evidence implicates vascular remodeling. Here, we identify the molecular mechanisms that contribute to vascular remodeling in CTEPH.Methods: Microarray data (GSE130391) for patients with CTEPH and healthy controls were downloaded from the Gene Expression Omnibus (GEO) and screened for differentially expressed genes (DEGs). DEGs were functionally annotated using Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A protein–protein interaction (PPI) network was constructed to identify hub genes. Finally, pulmonary artery samples were harvested from patients with CTEPH (n = 10) and from controls (n = 10) and primary vascular smooth muscle cells (VSMCs) were cultured. Effects of the proto-oncogene FOS on VSMC proliferation and migration were assessed using expression and knockdown studies.Results: We detected a total of 292 DEGs, including 151 upregulated and 141 downregulated genes. GO analysis revealed enrichment of DEGs in biological processes of signal transduction, response to lipopolysaccharide, signal transduction, and myeloid dendritic cell differentiation. Molecular function analysis revealed enrichment in tumor necrosis factor (TNF)-activated receptor activity, transcriptional activator activity, and protein homodimerization activity. The expression of TNF-α and its receptor (sTNFR1 and sTNFR2) were significantly higher in CTEPH group, compared with control group. KEGG pathway analysis revealed enrichment in salmonella infection, pathways in cancer, osteoclast differentiation, and cytokine-cytokine receptor interaction. Hub genes in the PPI included FOS, suggesting an important role for this gene in vascular remodeling in CTEPH. Primary VSMCs derived from patients with CTEPH showed increased FOS expression and high proliferation and migration, which was attenuated by FOS inhibition. In control VSMCs, TNF-α treatment increased proliferation and migration, which FOS inhibition likewise attenuated.Conclusion: TNF-α drives CTEPH pathogenesis by promoting VSMC proliferation and migration via increased FOS expression. These results advance our understanding of the molecular mechanisms of vascular remodeling in CTEPH, and may inform the development of new therapeutic targets.

Abstract 212: MicroRNA-663 is a Novel Regulator of Human Vascular Smooth Muscle Cell Phenotypic Switch in vitro and Neointimal Formation in vivo

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Pan Li ◽  
Bing Yi ◽  
Qing Qin ◽  
Ming Chen ◽  
Xiaohua You ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Marker Genes ◽  
Phenotypic Switch ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Background Abnormal phenotypic switch of vascular smooth muscle cell (VSMC) is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty. Recently, microRNAs (miRNAs) emerge as critical regulators for vascular smooth muscle cell (VSMC) function. Our initial study identified miR-663 as one of the most sharply downregulated miRNAs in human proliferative aortic smooth muscle cells. Hypothesis MiR-663 is implicated in human VSMC phenotypic switch and the development of neointima formation. Methods and Results By using quantitative real-time PCR (qRT-PCR), we found that microRNA-663 (miR-663) was significantly downregulated in cultured human aortic VSMCs upon platelet-derived growth factor (PDGF) treatment, whereas its expression was markedly increased during VSMC differentiation as induced by either retinoid acid or SMC differentiation medium, a condition which induces SMC differentiation and inhibits cell proliferation. Furthermore, we demonstrated that overexpression of miR-663 significantly increased the expression of VSMC differentiation marker genes, such as SM22α, SM α-action, calponin, and SM myosin heavy chain, suggesting that miR-663 is a novel modulator implicated in human VSMC phenotypic switch. Moreover, miR-663 potently inhibited PDGF induced VSMC proliferation and migration. Mechanistically, we identified JunB as a downstream target of miR-663 in human VSMCs. Indeed, overexpression of miR-663 markedly inhibited the expression of the transcription factor JunB as well as its downstream molecules including matrix metallopeptidase-9 (MMP-9) and myosin light chain-9 (Myl9), thus inhibiting VSMC proliferation and migration. Finally, we showed that adeno-miR-663 markedly suppressed the neointimal lesion formation by approximately 50% in mice after vascular injury induced by carotid artery ligation, specifically via decreased JunB expression. Conclusion These results indicate that miR-663 is a novel modulator implicated in human VSMC phenotypic switch through targeting JunB expression and suggest that specific modulation of miR-663 in human VSMCs may represent a novel and attractive approach for the treatment of vascular proliferative diseases.

scholarly journals Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

2018 ◽  
Vol 50 (5) ◽  
pp. 1740-1753 ◽  
Author(s):  
Shoucui Gao ◽  
Liran Xu ◽  
Yali Zhang ◽  
Qingqing Yu ◽  
Jiayan Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Atherosclerotic Lesion ◽  
Cell Counting ◽  
Matrix Metalloproteinase 2 ◽  
Aortic Lesion ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) are key steps in the progression of atherosclerosis. The aim of the present study was to investigate the potential roles of salusin-α in the functions of VSMCs during the development of atherosclerosis. Methods: In vivo, the effects of salusin-α on atherogenesis were examined in rabbits fed a cholesterol diet. The aortas were en face stained with Sudan IV to evaluate the gross atherosclerotic lesion size. The cellular components of atherosclerotic plaques were analyzed by immunohistochemical methods. In vitro, Cell Counting Kit-8 and wound-healing assays were used to assess the effects of salusin-α on VSMC proliferation and migration. In addition, western blotting was used to evaluate the total and phosphorylated levels of Akt (also known as protein kinase B) and mammalian target of rapamycin (mTOR) in VSMCs. Results: Salusin-α infusion significantly reduced the aortic lesion areas of atherosclerosis, with a 39% reduction in the aortic arch, a 71% reduction in the thoracic aorta, and a 71% reduction in the abdominal aorta; plasma lipid levels were unaffected. Immunohistochemical staining showed that salusin-α decreased both macrophage- and VSMC-positively stained areas in atherosclerotic lesions by 54% and 69%, cell proliferative activity in the intima and media of arteriosclerotic lesions, and matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in plaques. Studies using cultured VSMCs showed that salusin-α decreased VSMC migration and proliferation via reduced phosphorylation of Akt and mTOR. Conclusion: Our data indicate that salusin-α suppresses the development of atherosclerosis by inhibiting VSMC proliferation and migration through the Akt/mTOR pathway.

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