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.

scholarly journals Midkine Promotes the Proliferation of Airway Smooth Muscle Cells Induced by LPS Through Notch2 Pathway

2021 ◽  
Author(s):  
Qi Feng Huang ◽  
Tang Deng ◽  
Lihua Li ◽  
Jin Qian ◽  
Qi Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Control Group ◽  
Airway Smooth Muscle Cells ◽  
Proliferation And Apoptosis

Abstract Background: Airway smooth muscle cells (ASMC) can produce a variety of cytokine during inflammation, causing changes in the components of the extracellular matrix, which are related to airway remodeling. Midkine (MK) can promote the chemotaxis of various inflammatory cells and release inflammatory factors. Whether Notch and Midkine together affect the proliferation and apoptosis of airway smooth muscle cells is unclear.Objective: To study the mechanism of Midkine on LPS-induced acute lung injury caused by airway smooth muscle cells.Methods: Airway smooth muscle cells were cultured in vitro and divided into 5 groups: control group, lipopolysaccharide group (LPS), Non-targeted siRNA group, MKsiRNA group, Notch inhibitor group (LY411575). The cell proliferation level was detected by CCK-8. The apoptosis level was detected by flow cytometry. The changes of cytokine in the Midkine/Notch2 signaling pathway were detected by Westernblot, qPCR and cellular immunofluorescence.Results: Midkine and Notch2 were highly expressed in the LPS group. MKsiRNA can effectively block the expression of Midkine induced by LPS while down-regulating the expression of Notch2. This result is the same as that of Notch inhibitor (LY411575). Exogenous Midkine promoted the proliferation of airway smooth muscle cells and reduced the rate of apoptosis in the LPS group. When the expression of Midkine was blocked, the proliferation of airway smooth muscle cells in the LPS group was significantly reduced, while apoptosis increased. Inhibiting the expression of Notch, the proliferation of airway smooth muscle cells in the LPS group decreased, and apoptosis increased.Conclusions: Midkine/Notch2 signaling pathway plays an important role in regulating airway smooth muscle cell proliferation and apoptosis in airway inflammation.

scholarly journals TIPE2 inhibits PDGF-BB-induced phenotype switching in airway smooth muscle cells through the PI3K/Akt signaling pathway

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Huiyuan Wang ◽  
Bo Zhong ◽  
Yan Geng ◽  
Juanjuan Hao ◽  
Qiaoyan Jin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Muscle Protein ◽  
Muscle Cells ◽  
Akt Signaling ◽  
Airway Smooth Muscle Cells ◽  
Akt Signaling Pathway ◽  
Phenotype Switching

Abstract Background Childhood asthma is a common respiratory disease characterized by airway inflammation. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) has been found to be involved in the progression of asthma. This study aimed to explore the role of TIPE2 in the regulation of airway smooth muscle cells (ASMCs), which are one of the main effector cells in the development of asthma. Materials and methods ASMCs were transfected with pcDNA3.0-TIPE2 or si-TIPE2 for 48 h and then treated with platelet-derived growth factor (PDGF)-BB. Cell proliferation of ASMCs was measured using the MTT assay. Cell migration of ASMCs was determined by a transwell assay. The mRNA expression levels of calponin and smooth muscle protein 22α (SM22α) were measured using qRT-PCR. The levels of TIPE2, calponin, SM22α, PI3K, p-PI3K, Akt, and p-Akt were detected by Western blotting. Results Our results showed that PDGF-BB treatment significantly reduced TIPE2 expression at both the mRNA and protein levels in ASMCs. Overexpression of TIPE2 inhibited PDGF-BB-induced ASMC proliferation and migration. In addition, overexpression of TIPE2 increased the expression of calponin and SM22α in PDGF-BB-stimulated ASMCs. However, an opposite effect was observed with TIPE2 knockdown. Furthermore, TIPE2 overexpression blocked PDGF-BB-induced phosphorylation of PI3K and Akt, whereas the expression of p-PI3K and p-Akt were aggravated by TIPE2 knockdown. Additionally, the effects of TIPE2 overexpression and TIPE2 knockdown were altered by IGF-1 and LY294002 treatments, respectively. Conclusions Our findings demonstrate that TIPE2 inhibits PDGF-BB-induced ASMC proliferation, migration, and phenotype switching via the PI3K/Akt signaling pathway. Thus, TIPE2 may be a potential therapeutic target for the treatment of asthma.

scholarly journals Scopoletin inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells by regulating NF-κκB signaling pathway

2022 ◽  
Vol 50 (1) ◽  
pp. 92-98
Author(s):  
Zhongxiang Fan ◽  
Dan Tang ◽  
Qiang Wu ◽  
Qun Huang ◽  
Jie Song ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Chronic Inflammatory Disease ◽  
Migration And Invasion ◽  
Airway Smooth Muscle Cells ◽  
And Migration

Background: Asthma is a common chronic inflammatory disease of the airway, and airway remodeling and the proliferation mechanism of airway smooth muscle cells (ASMCs) is of great significance to combat this disease.Objective: To assess possible effects of scopoletin on asthma and the potential signaling pathway.Materials and methods: ASMCs were treated PDGF-BB and scopoletin and subjected to cell viability detection by CCK-8 assay. Cell migration of ASMCs was determined by a wound closure assay and transwell assay. The protein level of MMP2, MMP9, calponin and α-SMA were measured using western blot. The levels of NF-κB signaling pathway were detected by Western blotting.Results: Scopoletin inhibited proliferation of PDGF-BB - induced ASMCs. Also it suppressed the migration and invasion of PDGF-BB - induced ASMCs. We further showed that Scopoletin regulated phenotypic transition of ASMCs. Mechanically, Scopoletin inhibited proliferation and invasion of ASMCs by regulating NF-κB signaling pathway.Conclusions: We therefore thought Scopoletin could serve as a promising drug 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.

scholarly journals Midkine Ameliorates the LPS-Induced Apoptosis of Airway Smooth Muscle Cells Through the Notch2 Pathway

2021 ◽  
Author(s):  
Huang Qifeng ◽  
Deng Tang ◽  
Li Lihua ◽  
Qian Jin ◽  
Li Qi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Cell Counting ◽  
Airway Smooth Muscle Cells ◽  
Extracellular Matrix Components ◽  
Proliferation And Apoptosis

Abstract Background: Airway smooth muscle cells (ASMCs) produce several cytokines during inflammation, causing changes in extracellular matrix components, leading to airway remodeling. Midkine (MK) promotes the chemotaxis of inflammatory cells and releases proinflammatory factors. Whether Notch and Midkine jointly affect the proliferation and apoptosis of ASMCs is unknown. This research aimed to study the role of MK in ASMCs using an LPS-induced acute lung injury model.Methods: ASMCs were cultured in vitro and divided into five groups according to treatment: control, lipopolysaccharide (LPS), non-target siRNA, MK siRNA, and g-secretase inhibitor LY411575. Cell proliferation was assessed using the Cell Counting Kit-8 assay. Apoptosis was measured by flow cytometry. Changes in the levels of cytokines related to the MK/Notch2 signaling pathway were detected by Western blotting, qPCR, and immunofluorescence.Results: LPS increased the mRNA and protein expression of MK and Notch2. MK silencing and LY411575 reduced this effect. LPS reduced the viability and increased the rate of apoptosis of ASMCs. This effect was attenuated by exogenous MK and enhanced by MK silencing and LY411575 treatment.Conclusions: The MK/Notch2 signaling pathway plays a regulatory role in ASMC proliferation and apoptosis in airway inflammation.

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.

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