scholarly journals Stimulation of Adenosine A2B Receptor Inhibits Endothelin-1-Induced Cardiac Fibroblast Proliferation and α-Smooth Muscle Actin Synthesis Through the cAMP/Epac/PI3K/Akt-Signaling Pathway

2017 ◽  
Vol 8 ◽  
Author(s):  
Sarawuth Phosri ◽  
Ajaree Arieyawong ◽  
Kwanchai Bunrukchai ◽  
Warisara Parichatikanond ◽  
Akiyuki Nishimura ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Signaling Pathway ◽  
Smooth Muscle Actin ◽  
Akt Signaling ◽  
Fibroblast Proliferation ◽  
Muscle Actin ◽  
Akt Signaling Pathway ◽  
A2b Receptor ◽  
Adenosine A2b ◽  
Stimulation Of

scholarly journals Galectin-1 inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells through the inactivation of PI3K/Akt signaling pathway

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xinfeng Pang ◽  
Jing Qiao
Keyword(s):  
Smooth Muscle ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Akt Signaling ◽  
Airway Smooth Muscle Cells ◽  
Akt Signaling Pathway ◽  
Phenotype Switching ◽  
And Migration ◽  
Proliferation And Migration

Abstract Childhood asthma is one of the most common chronic childhood diseases. Platelet-derived growth factor BB (PDGF-BB) induced airway smooth muscle cell (ASMC) proliferation and migration are involved in the pathogenesis of asthma. Galectin-1 (Gal-1) is a glycan-binding protein that has been found to be involved in the progression of asthma. However, the mechanism remains unclear. In the current study, we aimed to evaluate the role of Gal-1 in regulating the phenotype switching of ASMCs, which is an important mechanism in the pathogenesis of asthma. Our results showed that Gal-1 was markedly down-regulated in the samples from asthma patients. In vitro study also proved that Gal-1 expression was decreased in PDGF-BB-stimulated ASMCs. In addition, Gal-1 overexpression significantly inhibited PDGF-BB-induced ASMCs proliferation and migration, while Gal-1 knockdown exhibits opposite effects of Gal-1 overexpression. The PDGF-BB-caused reductions in expressions of α-smooth muscle actin (α-SMA), specific muscle myosin heavy chain (SM-MHC), and calponin were elevated by Gal-1 overexpression, but were deteriorated by Gal-1 knockdown in ASMCs. Furthermore, overexpression of Gal-1 inhibited PDGF-BB-stimulated PI3K/Akt activation in ASMCs. Notably, treatment with IGF-1, an activator of PI3K, reversed the effects of Gal-1 on ASMCs proliferation, migration, and phenotype switching. In conclusion, these findings showed that Gal-1 exerted inhibitory effects on PDGF-BB-stimulated proliferation, migration, and phenotype switching of ASMCs via inhibiting the PI3K/Akt signaling pathway. Thus, Gal-1 might be a promising target for the treatment of asthma.

miR-223 Promotes Smooth Muscle Cell Proliferation and Atherosclerotic Plaque Formation by Inhibiting Phosphatase and Tensin Homolog (PTEN)/ Phosphatidylinositol 3-Kinase (PI3K) and Protein Kinase B (AKT) Signaling Pathway

2020 ◽  
Vol 10 (5) ◽  
pp. 719-723
Author(s):  
Xiaofang Tao ◽  
Nianhua Fei
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Plaque Formation ◽  
Akt Signaling Pathway ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Sd Rats ◽  
Vsmcs Proliferation

Abnormal vascular smooth muscle cells (VSMCs) proliferation is the pathological basis of atherosclerosis (AS) pathogenesis. miR-223 is abnormally expressed in AS plaques and affects the proliferation of VSMCs, but the mechanism of miR-223 affecting the proliferation of VSMCs is unclear. Our study intends to investigate the mechanism of miR-223 in VSMCs proliferation and AS formation. Healthy SD rats and miR-223 knockout SD rats took high-fat diet to induce AS model. Oil red O staining was done to observe AS formation. miR-223 mimics/NC was transferred to VSMCs followed by analysis of miR-214 expression by real-time PCR, cell proliferation by CCK8 assay, phosphatase and tensin homolog gene (PTEN) level by Western blot detection. Compared with control group, after knocking out miR-223, the AS level was significantly decreased and PTEN expression was significantly elevated (P < 0 05). After transfection of miR-223 mimics into VSMCs, PTEN expression protein was significantly decreased and the number of cells was increased (P < 0 05). In addition, the luciferase signal of miR-223 mimics and pmirGLO-PTEN-3 UTR-wt co-transfection group was significantly reduced (P < 0 05). miR-223 promotes VSMCs proliferation and AS plaque formation by targeting PTEN/PI3K/Akt signaling pathway.

MKL1 mediates TGF-β1-induced α-smooth muscle actin expression in human renal epithelial cells

2008 ◽  
Vol 294 (5) ◽  
pp. F1116-F1128 ◽  
Author(s):  
Gerard Elberg ◽  
Lijuan Chen ◽  
Dorit Elberg ◽  
Michael D. Chan ◽  
Charlotte J. Logan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Primary Cultures ◽  
Muscle Actin ◽  
Mesenchymal Transition ◽  
Endogenous Expression ◽  
Tgf Β1 ◽  
Stimulation Of

Transforming growth factor-β1 (TGF-β1) is known to induce epithelial-mesenchymal transition in the kidney, a process involved in tubulointerstitial fibrosis. We hypothesized that a coactivator of the serum response factor (SRF), megakaryoblastic leukemia factor-1 (MKL1), stimulates α-smooth muscle actin (α-SMA) transcription in primary cultures of renal tubular epithelial cells (RTC), which convert into myofibroblasts on treatment with TGF-β1. Herein, we study the effect of MKL1 expression on α-SMA in these cells. We demonstrate that TGF-β1 stimulation of α-SMA transcription is mediated through CC(A/T)6-rich GG elements known to bind to SRF. These elements also mediate the MKL1 effect that dramatically activates α-SMA transcription in serum-free media. MKL1 fused to green fluorescent protein localizes to the nucleus and induces α-SMA expression regardless of treatment with TGF-β1. Using proteasome inhibitors, we also demonstrate that the proteolytic ubiquitin pathway regulates MKL1 expression. These data indicate that MKL1 overexpression is sufficient to induce α-SMA expression. Inhibition of endogenous expression of MKL1 by small interfering RNA abolishes TGF-β1 stimulation of α-SMA expression. Therefore, MKL1 is also absolutely required for TGF-β1 stimulation of α-SMA expression. Western blot and immunofluorescence analysis show that overexpressed and endogenous MKL1 are located in the nucleus in non-stimulated RTC. Chromatin immunoprecipitation assay demonstrates that TGF-β1 induces binding of endogenous SRF and MKL1 to the α-SMA promoter in chromatin. Since MKL1 constitutes a potent factor regulating α-SMA expression, modulation of endogenous MKL1 expression or activity may have a profound effect on myofibroblast formation and function in the kidney.

scholarly journals The Antiapoptotic Gene mcl-1 Is Up-Regulated by the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway through a Transcription Factor Complex Containing CREB

1999 ◽  
Vol 19 (9) ◽  
pp. 6195-6206 ◽  
Author(s):  
Ju-Ming Wang ◽  
Jyh-Rong Chao ◽  
Wannhsin Chen ◽  
Min-Liang Kuo ◽  
Jeffrey J.-Y. Yen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Signaling Pathway ◽  
Reporter Gene ◽  
Akt Signaling ◽  
Binding Activity ◽  
Akt Signaling Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Transcription Factor Complex ◽  
Stimulation Of

ABSTRACT mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3) signaling pathways and plays an important role in the viability response of these cytokines. In this study, we demonstrated that cytokine stimulation of mcl-1 mRNA and protein expression were attenuated by pretreatment of cells with phosphatidylinositol 3-kinase (PI3-K) inhibitors. Reporter gene assays further showed that the PI3-K/Akt signaling pathway was involved in IL-3 activation of mcl-1 gene transcription. Analysis of the mcl-1 promoter revealed that both promoter elements, SIE at position −87 and CRE-2 at −70, contribute to IL-3 stimulation of mcl-1 gene expression. Although either the SIE site or the CRE-2 site alone was sufficient to confer IL-3 inducibility on a heterologous promoter, only IL-3 activation of the CRE-2 reporter was mediated via the PI3-K/Akt pathway. The SIE binding activity was constitutively high in cells deprived of or stimulated by IL-3. In contrast, the CRE-2 binding activity was low in cytokine-starved cells and was strongly induced within 1 h following cytokine treatment of cells. In addition, cytokine induction of the CRE-2 but not of the SIE binding activity was dependent on activation of the PI3-K/Akt signaling pathway. Lastly, we showed that CREB was one component of the CRE-2 binding complex and played a role in IL-3 activation of themcl-1 reporter gene. Taken together, our results suggest that both PI3-K/Akt-dependent and -independent pathways contribute to the IL-3 activation of mcl-1 gene expression. Activation ofmcl-1 by the PI3-K/Akt-dependent pathway is through a transcription factor complex containing CREB.

scholarly journals MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

2018 ◽  
Vol 50 (6) ◽  
pp. 2365-2389 ◽  
Author(s):  
Ying  Liu ◽  
Yi Miao ◽  
Xin Gao ◽  
Yuan-Yuan Wang ◽  
Huan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Bioinformatics Analysis ◽  
Airway Remodeling ◽  
Akt Signaling ◽  
Airway Smooth Muscle Cells ◽  
Akt Signaling Pathway ◽  
Tgf Β1

Background/Aims: The etiology of asthma, which is a complicated disorder with various symptoms, including wheezing, coughing, and airflow obstruction, remains poorly understood. In addition, the effects of microRNAs (miRs) have not been explored. This study explored the effect of microRNA-200a (miR-200a) on airway smooth muscle cells (ASMCs) and airway remodeling in asthmatic mice. Furthermore, we speculated that miR-200a achieves its effect by targeting FOXC1 via the PI3K/AKT signaling pathway based on differentially expressed gene screening, target miR predictions and a bioinformatics analysis. Methods: Eighty mice were assigned to a saline group or an ovalbumin (OVA) group, and the OVA group was transfected with a series of inhibitors, activators, and siRNAs to test the established mouse model. Airway reactivity and the ratio of eosinophils (EOSs) to leukocytes were detected. An ELISA was adopted to measure the levels of interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor (TNF)-α, and immunoglobulin E (IgE). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1, TGF-β1 and p-AKT in ASMCs. Finally, CCK-8 assays were performed to detect cell proliferation and flow cytometry to detect apoptosis and cell cycle entry. Results: The bioinformatics analysis indicated that miR-200a mediated the PI3K/AKT signaling pathway by targeting FOXC1. In addition, mouse models of asthma were established. An elevated expression of miR-200a, a decreased mRNA and protein expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1 and TGF-β1, a decreased expression of p-AKT, suppressed cell proliferation, accelerated apoptosis, and an increased number of cells at the G0/G1 phase were observed following the upregulation of miR-200a and downregulation of FOXC1. Conclusion: The overexpression of miR-200a may downregulate FOXC1, thereby inhibiting the activation of the PI3K/AKT signaling pathway and ultimately suppressing ASMC proliferation and airway remodeling in asthmatic mice. This evidence supports the potential that miR-200a represents a new approach to treating asthma.

Ligustrazine Suppresses Platelet-Derived Growth Factor-BB-Induced Pulmonary Artery Smooth Muscle Cell Proliferation and Inflammation by Regulating the PI3K/AKT Signaling Pathway

2021 ◽  
pp. 1-23
Author(s):  
Huiping Huang ◽  
Lingjin Kong ◽  
Shaohua Luan ◽  
Chuanzong Qi ◽  
Fanrong Wu
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Right Ventricular ◽  
Signaling Pathway ◽  
Ventricular Hypertrophy ◽  
Akt Signaling ◽  
Platelet Derived Growth Factor ◽  
Akt Signaling Pathway ◽  
Pulmonary Artery Smooth Muscle

Pulmonary arterial hypertension (PAH) is a serious pulmonary vascular disease. Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role in the course of this disease. Ligustrazine is an alkaloid monomer extracted from the rhizome of the herb Ligusticum chuanxiong. It is often used to treat cardiovascular diseases, but its effect on PAH has rarely been reported. This study aims to explore the protective effect and mechanism of ligustrazine on PAH. In the in vivo experiment, monocrotaline (MCT) was used to induce PAH in rats, and then ligustrazine (40, 80, 160 mg/kg/day) or sildenafil (25 mg/kg/day) was administered. Four weeks later, hemodynamic changes, right ventricular hypertrophy index, lung morphological characteristics, inflammatory factors, phosphoinositide 3-kinase (PI3K), and AKT expression were evaluated. In addition, primary rat PASMCs were extracted by the tissue adhesion method, a proliferation model was established with platelet-derived growth factor-BB (PDGF-BB), and the cells were treated with ligustrazine to investigate its effects on cell proliferation, inflammation, and cell cycle distribution. The results indicate that ligustrazine can markedly alleviate right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodeling, and inflammation caused by MCT, and that it decreased PI3K and AKT phosphorylation expression. Moreover, ligustrazine can inhibit the proliferation and inflammation of PASMCs and arrest the progression of G0/G1 to S phase through the PI3K/AKT signaling pathway. Therefore, we conclude that ligustrazine may inhibit the proliferation and inflammation of PASMCs by regulating the activation of the PI3K/AKT signaling pathway, thereby attenuating MCT-induced PAH in rats. Collectively, these findings suggest that ligustrazine may be a promising therapeutic for PAH.

scholarly journals The PDE1A-PKCα Signaling Pathway Is Involved in the Upregulation of α-Smooth Muscle Actin by TGF-β1 in Adventitial Fibroblasts

2010 ◽  
Vol 47 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Hai-Yan Zhou ◽  
Wen-Dong Chen ◽  
Ding-Liang Zhu ◽  
Ling-Yun Wu ◽  
Jia Zhang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Signaling Pathway ◽  
Smooth Muscle Actin ◽  
Muscle Actin ◽  
Tgf Beta ◽  
Alpha Smooth Muscle Actin ◽  
Adventitial Fibroblasts ◽  
Pkc Alpha
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