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.

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 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.

scholarly journals MicroRNA-142 Inhibits Proliferation and Promotes Apoptosis in Airway Smooth Muscle Cells During Airway Remodeling in Asthmatic Rats via the Inhibition of TGF-β -Dependent EGFR Signaling Pathway

2018 ◽  
Vol 47 (4) ◽  
pp. 1682-1695 ◽  
Author(s):  
Jing Wang ◽  
Hu-Shan Wang ◽  
Zhen-Bo Su
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Egfr Signaling ◽  
Expression Levels ◽  
Egfr Signaling Pathway

Background/Aims: Asthma is a heterogeneous disease characterized by chronic airway inflammation resulting from airway hyper-responsiveness to diverse stimuli. In this study, we investigated whether microRNA-142 (miR-142) expression affects proliferation and apoptosis in airway smooth muscle cells (ASMCs) during airway remodeling in asthmatic rats. Methods: Thirty six Wistar rats were randomly classified into a control group and an model group. miR-142 mimics and inhibitors were constructed, and ASMCs were transfected using liposomes according to the following groups: blank, negative control (NC), miR-142 mimics, miR-142 inhibitors, si-TGF-β and miR-142 inhibitors + si-TGF-β. We verified that miR-142 targets TGF-β using a dual-luciferase reporter assay. The expression levels of miR-142, TGF-β, EGFR and apoptosis signaling pathway-related genes were determined using RT-qPCR and western blotting. Changes in cell proliferation, cell cycle progression and apoptosis were analyzed using MTT assays and flow cytometry. Results: Rats with asthma had higher expression levels of EGFR and Akt and lower miR-142 levels. miR-142 was negatively correlated with TGF-β expression. In ASMCs, the expression of TGF-β, EGFR, Akt, phosphorylated-Akt (p-Akt), Bcl-2 and Bcl-xl and the rate of early apoptosis were decreased while expression of Bax and p21 and the proliferation rate were elevated with the upregulation of miR-142. The opposite results were observed with the downregulation of miR-142. Finally, the proliferative rate was decreased while the apoptosis rate was increased and expression levels of EGFR, Akt, p-Akt, Bcl-2 and Bcl-xl were reduced while Bax and p21 were elevated in the ASMCs transfected with miR-142 inhibitors and si-TGF-β. Conclusion: The results of our study suggest that miR-142 inhibits proliferation and promotes apoptosis in ASMCs during airway remodeling in asthmatic rats by inhibiting TGF-β expression via a mechanism involving the EGFR signaling pathway.

scholarly journals Recombinant Rat CC10 Protein Inhibits PDGF-Induced Airway Smooth Muscle Cells Proliferation and Migration

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Wei ◽  
Yu-Dong Xu ◽  
Lei-Miao Yin ◽  
Yu Wang ◽  
Jun Ran ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cyclin D1 ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Clara Cell ◽  
Airway Smooth Muscle Cells ◽  
And Migration ◽  
Proliferation And Migration

Abnormal migration and proliferation of airway smooth muscle cells (ASMCs) in the airway cause airway wall thickening, which is strongly related with the development of airway remodeling in asthma. Clara cell 10 kDa protein (CC10), which is secreted by the epithelial clara cells of the pulmonary airways, plays an important role in the regulation of immunological and inflammatory processes. Previous studies suggested that CC10 protein had great protective effects against inflammation in asthma. However, the effects of CC10 protein on ASMCs migration and proliferation in airway remodeling were poorly understood. In this study, we constructed the pET-22b-CC10 recombinant plasmid, induced expression and purified the recombinant rat CC10 protein fromE. coliby Ni2+affinity chromatography and ion exchange chromatography purification. We investigated the effect of recombinant rat CC10 protein on platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation and migration. Our results demonstrated that the recombinant CC10 protein could inhibit PDGF-BB-induced cell viability, proliferation and migration. Western blot analysis showed that PDGF-BB-induced activation of cyclin D1 was inhibited by CC10. These findings implicated that CC10 could inhibit increased ASMCs proliferation, and migration induced by PDGF-BB, and this suppression effect might be associated with inhibition of cyclin D1 expression, which might offer hope for the future treatment of airway remodeling.

Urokinase potentiates PDGF-induced chemotaxis of human airway smooth muscle cells

2003 ◽  
Vol 284 (6) ◽  
pp. L1020-L1026 ◽  
Author(s):  
Stephen M. Carlin ◽  
Michael Roth ◽  
Judith L. Black
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Kinase Inhibitor ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Mek Inhibitor ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Human Airway

We investigated the chemotactic action of PDGF and urokinase on human airway smooth muscle (HASM) cells in culture. Cells were put in collagen-coated transwells with 8-μm perforations, incubated for 4 h with test compounds, then fixed, stained, and counted as migrated nuclei by microscopy. Cells from all culture conditions showed some basal migration (migration in the absence of stimuli during the assay), but cells preincubated for 24 h in 10% FBS or 20 ng/ml PDGF showed higher basal migration than cells quiesced in 1% FBS. PDGFBB, PDGFAA, and PDGFABwere all chemotactic when added during the assay. PDGF chemotaxis was blocked by the phosphatidyl 3′-kinase inhibitor LY-294002, the MEK inhibitor U-0126, PGE2, formoterol, pertussis toxin, and the Rho kinase inhibitor Y-27632. Urokinase alone had no stimulatory effect on migration of quiescent cells but caused a dose-dependent potentiation of chemotaxis toward PDGF. Urokinase also potentiated the elevated basal migration of cells pretreated in 10% FBS or PDGF. This potentiating effect of urokinase appears to be novel. We conclude that PDGF and similar cytokines may be important factors in airway remodeling by redistribution of smooth muscle cells during inflammation and that urokinase may be important in potentiating the response.

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