scholarly journals Qufeng Xuanbi Formula ameliorates airway remodeling in asthmatic mice by suppressing airway smooth muscle cells proliferation through MEK/ERK signaling pathway

2021 ◽  
Author(s):  
Bohan Wang ◽  
Lingling Tang ◽  
Suofang Shi ◽  
Ying Yang ◽  
Xianhong Sun ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Lung Tissue ◽  
Airway Remodeling ◽  
Erk Signaling ◽  
Immunofluorescent Staining ◽  
Control Group ◽  
Airway Smooth Muscle Cells ◽  
Therapeutic Effects ◽  
Protein Expressions

Abstract BackgroundAsthma is a common chronic respiratory disease. Qufeng Xuanbi Formula (QFXBF), a Chinese herbal decoction, has shown efficiency for the management of asthma. The purpose of current study is to investigate the potential therapeutic effects of QFXBF for the treatment of asthma both in vitro and in vivo. MethodsPDGF-induced ASMCs proliferation model and MTT assay have been applied for exploring the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, OVA group, High QFXBF group, Low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). The mouse allergic asthma model has been established by intranasally administered ovalbumin (OVA) sensitization method. Morphological changes of the lung tissue have been examined by hematoxylin and eosin (H&E) staining and Masson’s staining. Finally, the protein expressions of α-SMA, PCNA, p-MEK1/2, MEK1/2, p-ERK1/2, and ERK1/2 in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. ResultsPDGF induced significant increase in viability of ASMCs. Compared with mice in control group, the airway walls and airway smooth muscle of mice in OVA group mice thickened, and the inflammatory cells around the bronchus increased significantly. Moreover, administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathologic changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment of QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA and PCNA. ConclusionQFXBF can inhibit the proliferation of ASMCs via suppressing the MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.

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.

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.

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 Estrogen receptors differentially regulate intracellular calcium handling in human nonasthmatic and asthmatic airway smooth muscle cells

2020 ◽  
Vol 318 (1) ◽  
pp. L112-L124 ◽  
Author(s):  
Sangeeta Bhallamudi ◽  
Jennifer Connell ◽  
Christina M Pabelick ◽  
Y. S. Prakash ◽  
Venkatachalem Sathish
Keyword(s):  
Smooth Muscle ◽  
Estrogen Receptors ◽  
Intracellular Calcium ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Clinical Findings ◽  
Calcium Handling ◽  
Airway Smooth Muscle Cells ◽  
Adult Women ◽  
Channel Inhibition

Asthma is defined as chronic inflammation of the airways and is characterized by airway remodeling, hyperresponsiveness, and acute bronchoconstriction of airway smooth muscle (ASM) cells. Clinical findings suggest a higher incidence and severity of asthma in adult women, indicating a concrete role of sex steroids in modulating the airway tone. Estrogen, a major female sex steroid mediates its role through estrogen receptors (ER) ERα and ERβ, which are shown to be expressed in human ASM, and their expression is upregulated in lung inflammation and asthma. Previous studies suggested rapid, nongenomic signaling of estrogen via ERs reduces intracellular calcium ([Ca2+]i), thereby promoting relaxation of ASM. However, long-term ER activation on [Ca2+]i regulation in human ASM during inflammation or in asthma is still not known. In Fura-2-loaded nonasthmatic and asthmatic human ASM cells, we found that prolonged (24 h) exposure to ERα agonist (PPT) increased [Ca2+]i response to histamine, whereas ERβ activation (WAY) led to decreased [Ca2+] compared with vehicle. This was further confirmed by ER overexpression and knockdown studies using various bronchoconstrictor agents. Interestingly, ERβ activation was more effective than 17β-estradiol in reducing [Ca2+]i responses in the presence of TNF-α or IL-13, while no observable changes were noticed with PPT in the presence of either cytokine. The [Ca2+]i-reducing effects of ERβ were mediated partially via L-type calcium channel inhibition and increased Ca2+ sequestration by sarcoplasmic reticulum. Overall, these data highlight the differential signaling of ERα and ERβ in ASM during inflammation. Specific ERβ activation reduces [Ca2+]i in the inflamed ASM cells and is likely to play a crucial role in regulating ASM contractility, thereby relaxing airways.

Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration

2006 ◽  
Vol 291 (5) ◽  
pp. C957-C965 ◽  
Author(s):  
Vasanthi Govindaraju ◽  
Marie-Claire Michoud ◽  
Mustafa Al-Chalabi ◽  
Pasquale Ferraro ◽  
William S. Powell ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Neutralizing Antibodies ◽  
Airway Remodeling ◽  
Fold Increase ◽  
Airway Smooth Muscle Cell ◽  
Interleukin 8 ◽  
Airway Smooth Muscle Cells ◽  
Cell Contraction ◽  
And Migration

In patients with cystic fibrosis (CF) and asthma, elevated levels of interleukin-8 (IL-8) are found in the airways. IL-8 is a CXC chemokine that is a chemoattractant for neutrophils through CXCR1 and CXCR2 G protein-coupled receptors. We hypothesized that IL-8 acts directly on airway smooth muscle cells (ASMC) in a way that may contribute to the enhanced airway responsiveness and airway remodeling observed in CF and asthma. The aim of this study was to determine whether human ASMC (HASMC) express functional IL-8 receptors (CXCR1 and CXCR2) linked to cell contraction and migration. Experiments were conducted on cells harvested from human lung specimens. Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2. Intracellular Ca2+ concentration ([Ca2+]i) increased from 115 to 170 nM in response to IL-8 (100 nM) and decreased after inhibition of phospholipase C (PLC) with U-73122. On blocking the receptors with specific neutralizing antibodies, changes in [Ca2+]i were abrogated. IL-8 also contracted the HASMC, decreasing the length of cells by 15%, and induced a 2.5-fold increase in migration. These results indicate that HASMC constitutively express functional CXCR1 and CXCR2 that mediate IL-8-triggered Ca2+ release, contraction, and migration. These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF.

scholarly journals Dandelion Extract Relaxes Mouse Airway Smooth Muscle by Blocking VDLCC and NSCC Channels

2020 ◽  
Author(s):  
zhao ping ◽  
Jia Liu ◽  
Qian Ming ◽  
Di Tian ◽  
Jingwen He ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Imaging System ◽  
Force Measurement ◽  
Medical Community ◽  
Mouse Lung ◽  
Airway Smooth Muscle Cells ◽  
Therapeutic Effects ◽  
Forced Oscillation Technique ◽  
System L

Abstract Background: Asthma is one of the main intractable diseases recognized by the international medical community. The current widely used bronchodilators for asthma—β2-adrenal receptor agonists—have limited therapeutic effects, necessitating the development of novel antiasthma drugs with increased efficacy and fewer adverse effects. In this study, we investigated the relaxant effects and underlying mechanism of an ethyl acetate extract from dandelion (EAED) on mouse airway smooth muscle.Methods: The effects of EAED on agonist-induced precontraction in mouse airway smooth muscle were evaluated with force measurement. Mouse lung slices were used to study the effects of EAED on bronchial smooth muscle. The intracellular Ca2+ concentration was measured using a calcium imaging system. L-type voltage-dependent calcium channel (VDLCC) and non-selective cationic channel (NSCC) currents were measured by patch-clamp. The lung functions of healthy and asthmatic mouse groups were assessed via the forced oscillation technique.Results: EAED inhibits acetylcholine-induced sustained contractions of whole airway smooth muscle by inhibiting VDLCCs, NSCCs, and some unknown channels, reduces the agonist-induced increase in the cytosolic free Ca2+ concentration in airway smooth muscle cells, blocks VDLCC and NSCC currents, and relieves the respiratory resistance of healthy and asthmatic mice.Conclusions: EAED may have potential beneficial effects on asthma attacks.

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.

Sign in / Sign up

Export Citation Format

Share Document