IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells

2000 ◽  
Vol 279 (1) ◽  
pp. C248-C256 ◽  
Author(s):  
Liu Hua Wei ◽  
Aaron T. Jacobs ◽  
Sidney M. Morris ◽  
Louis J. Ignarro
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Growth ◽  
Muscle Cells ◽  
Protein Levels ◽  
Ifn Γ ◽  
Arginase Ii ◽  
Arginase I

The objectives of this study were to determine whether rat aortic smooth muscle cells (RASMC) express arginase and to elucidate the possible mechanisms involved in the regulation of arginase expression. The results show that RASMC contain basal arginase I (AI) activity, which is significantly enhanced by stimulating the cells with either interleukin (IL)-4 or IL-13, but arginase II (AII) expression was not detected under any condition studied here. We further investigated the signal transduction pathways responsible for AI induction. AI mRNA and protein levels were enhanced by addition of forskolin (1 μM) and inhibited by H-89 (30 μM), suggesting positive regulation of AI by a protein kinase A pathway. Genistein (10 μg/ml) and sodium orthovanadate (Na3VO4; 10 μM) were used to investigate the role of tyrosine phosphorylation in the control of AI expression. Genistein inhibited, whereas Na3VO4enhanced the induction of AI by IL-4 or IL-13. Along with immunoprecipitation and immunoblot analyses, these data implicate the JAK/STAT6 pathway in AI regulation. Dexamethasone (Dex) and interferon (IFN)-γ were investigated for their effects on AI induction. Dex (1 μM) and IFN-γ (100 U/ml) alone had no effect on basal AI expression in RASMC, but both reduced AI induction by IL-4 and IL-13. In combination, Dex and IFN-γ abolished AI induction by IL-4 and IL-13. Finally, both IL-4 and IL-13 significantly increased RASMC DNA synthesis as monitored by [3H]thymidine incorporation, demonstrating that upregulation of AI is correlated with an increase in cell proliferation. Blockade of AI induction by IFN-γ, H-89, or genistein also blocked the increase in cell proliferation. These observations are consistent with the possibility that upregulation of AI might play an important role in the pathophysiology of vascular disorders characterized by excessive smooth muscle growth.

scholarly journals LncRNA SCIRT is downregulated in atherosclerosis and suppresses the proliferation of human aortic smooth muscle cells (HAOSMCs) by sponging miR-146a in cytoplasm

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wenhui Gao ◽  
Rong Li ◽  
Jingjing Yu ◽  
Xijie He ◽  
Duo Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cancer Biology ◽  
Direct Interaction ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Brdu Assay

Abstract Background SCIRT has been characterized as a key player in cancer biology, while its role in other human diseases is unclear. This study explored its role in atherosclerosis, with a specific focus on its interaction with SCIRT and miR-146a. Methods The expression of SCIRT and miR-146a in atherosclerosis-affected tissues and healthy tissues from 56 atherosclerosis patients were analyzed by RT-qPCR. The expression of SCIRT in nuclear and cytoplasm samples was detected by RNA fractionation assay. The direct interaction between SCIRT and miR-146a was detected by RNA pull-down assay. SCIRT and miR-146a were overexpressed in human aortic smooth muscle cells (HAOSMCs) to study the crosstalk between them. The role of SCIRT and miR-146a in the proliferation of HAOSMCs was analyzed with BrdU assay. Results SCIRT was downregulated by atherosclerosis, while miR-146a was upregulated by atherosclerosis. SCIRT was detected in both cytoplasm and nuclear samples, and it directly interacted with miR-146a. In HAOSMCs, overexpression of SCIRT and miR-146a did not affect the expression of each other. Interestingly, SCIRT suppressed the proliferation of HAOSMCs and reduced the enhancing effects of miR-146a on cell proliferation. Conclusion Therefore, SCIRT is downregulated in atherosclerosis and it suppresses the proliferation of HAOSMCs by sponging miR-146a in cytoplasm.

Long noncoding RNA Hoxaas3 contributes to hypoxia-induced pulmonary artery smooth muscle cell proliferation

2018 ◽  
Vol 115 (3) ◽  
pp. 647-657 ◽  
Author(s):  
Hongyue Zhang ◽  
Ying Liu ◽  
Lixin Yan ◽  
Siqi Wang ◽  
Min Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Noncoding Rna ◽  
Muscle Cells ◽  
Cell Cycle Distribution ◽  
Hoxa Cluster ◽  
Protein Levels ◽  
Pulmonary Artery Smooth Muscle

Abstract Aims Long noncoding RNAs (lncRNAs) are involved in the regulation of vascular smooth muscle cells and cardiovascular pathology. However, the contribution of lncRNAs to pulmonary hypertension (PH) remains largely unknown. The over-proliferation of pulmonary artery smooth muscle cells (PASMCs) causes pulmonary arterial smooth muscle hypertrophy and stenosis of the pulmonary vascular lumen, resulting in PH. Here, we investigated the biological role of a novel lncRNA, Hoxa cluster antisense RNA 3 (Hoxaas3), in the regulation of cell proliferation in PH. Methods and results Hoxaas3 was up-regulated in the lung vasculature of hypoxic mice and in PASMCs under hypoxic conditions. Histone H3 Lysine 9 acetylation of Hoxaas3 promoted gene expression. Moreover, high expression of Hoxaas3 was associated with cell proliferation and modulated cell cycle distribution by up-regulating Homeobox a3 at the mRNA and protein levels. Conclusion This study defined the role and mechanism of action of Hoxaas3 in the regulation of cell proliferation in PH, which should facilitate the development of new therapeutic strategies for the treatment of this disease.

scholarly journals Abl regulates smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 activation

2012 ◽  
Vol 302 (7) ◽  
pp. C1026-C1034 ◽  
Author(s):  
Li Jia ◽  
Ruping Wang ◽  
Dale D. Tang
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Actin Polymerization ◽  
Muscle Cells ◽  
Smooth Muscle Cell Proliferation ◽  
Actin Dynamics

Abl is a nonreceptor tyrosine kinase that has a role in regulating migration and adhesion of nonmuscle cells as well as smooth muscle contraction. The role of Abl in smooth muscle cell proliferation has not been investigated. In this study, treatment with endothelin-1 (ET-1) and platelet-derived growth factor (PDGF) increased Abl phosphorylation at Tyr412 (an indication of Abl activation) in vascular smooth muscle cells. To assess the role of Abl in smooth muscle cell proliferation, we generated stable Abl knockdown cells by using lentivirus-mediated RNA interference. ET-1- and PDGF-induced cell proliferation was attenuated in Abl knockdown cells compared with cells expressing control shRNA and uninfected cells. Abl silencing also arrested cell cycle progression from G0/G1 to S phase. Furthermore, activation of smooth muscle cells with ET-1 and PDGF induced phosphorylation of ERK1/2 and Akt. Abl knockdown attenuated ERK1/2 phosphorylation in smooth muscle cells stimulated with ET-1 and PDGF. However, Akt phosphorylation upon stimulation with ET-1 and PDGF was not reduced. Because Abl is known to regulate actin polymerization in smooth muscle, we also evaluated the effects of inhibition of actin polymerization on phosphorylation of ERK1/2. Pretreatment with the actin polymerization inhibitor latrunculin-A also blocked ERK1/2 phosphorylation during activation with ET-1 and PDGF. The results suggest that Abl may regulate smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 phosphorylation during mitogenic activation.

The role of WNT/b-catenin signaling in smooth muscle cells during lung development and repair

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
A Moiseenko ◽  
E El Agha ◽  
B MacKenzie ◽  
S De Langhe ◽  
S Bellusci
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Lung Development ◽  
Muscle Cells

Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

1990 ◽  
Vol 63 (02) ◽  
pp. 291-297 ◽  
Author(s):  
Herm-Jan M Brinkman ◽  
Marijke F van Buul-Worteiboer ◽  
Jan A van Mourik
Keyword(s):  
Cell Proliferation ◽  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Muscle Cells ◽  
Smooth Muscle Cell Proliferation

SummaryWe observed that the growth of human umbilical arterysmooth muscle cells was inhibited by the phospholipase A2 inhibitors p-bromophenacylbromide and mepacrine. Thesefindings suggest that fatty acid metabolism might be integrated in the control mechanism of vascular smooth muscle cell proliferation. To identify eicosanoids possibly involved in this process, we studied both the metabolism of arachidonic acid of these cells in more detail and the effect of certain arachidonic acid metabolites on smooth muscle cells growth. We found no evidence for the conversion of arachidonic acid via the lipoxygenase pathway. In contrast, arachidonic acid was rapidly converted via the cyclooxy-genase pathway. The following metabolites were identified: prostaglandin E2 (PGE2), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), 12-hydroxyheptadecatrienoic acid (12-HHT) and 11-hydroxyeicosatetetraenoic acid (11-HETE). PGE2 was the major metabolite detected. Arachidonic acid metabolites were only found in the culture medium, not in the cell. After synthesis, 11-HETE was cleared from the culture medium. We have previously reported that PGE2 inhibits the serum-induced [3H]-thymidine incorporation of growth-arrested human umbilical artery smooth muscle cells. Here we show that also 11-HETEexerts this inhibitory property. Thus, our data suggeststhat human umbilical artery smooth muscle cells convert arachidonic acid only via the cyclooxygenase pathway. Certain metabolites produced by this pathway, including PGE2 and 11-HETE, may inhibit vascular smooth muscle cell proliferation.

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