scholarly journals TNFSF14, a novel target of miR‐326, facilitates airway remodeling in airway smooth muscle cells via inducing extracellular matrix protein deposition and proliferation

2020 ◽  
Vol 36 (7) ◽  
pp. 508-514
Author(s):  
Hui Zhang ◽  
Huan‐Li Yan ◽  
Xiang‐Yu Li ◽  
Yi‐Nan Guo
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Matrix Protein ◽  
Airway Remodeling ◽  
Extracellular Matrix Protein ◽  
Airway Smooth Muscle Cells ◽  
Protein Deposition ◽  
Novel Target

Rhinovirus infection induces extracellular matrix protein deposition in asthmatic and nonasthmatic airway smooth muscle cells

2011 ◽  
Vol 300 (6) ◽  
pp. L951-L957 ◽  
Author(s):  
Curtis Kuo ◽  
Sam Lim ◽  
Nicholas J. C. King ◽  
Sebastian L. Johnston ◽  
Janette K. Burgess ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Matrix Protein ◽  
Viral Infections ◽  
Airway Remodeling ◽  
Extracellular Matrix Protein ◽  
Airway Smooth Muscle Cells ◽  
Increased Risk

Airway remodeling, which includes increases in the extracellular matrix (ECM), is a characteristic feature of asthma and is correlated to disease severity. Rhinovirus (RV) infections are associated with increased risk of asthma development in young children and are the most common cause of asthma exacerbations. We examined whether viral infections can increase ECM deposition and whether this increased ECM modulates cell proliferation and migration. RV infection of nonasthmatic airway smooth muscle (ASM) cells significantly increased the deposition of fibronectin (40% increase, n = 12) and perlecan (80% increase, n = 14), while infection of asthmatic ASM cells significantly increased fibronectin (75% increase, n = 9) and collagen IV (15% increase, n = 9). We then treated the ASM cells with the Toll-like receptor (TLR) agonists polyinosinic:polycytidylic acid, imiquimod, and pure RV RNA and were able to show that the mechanism through which RV induced ECM deposition was via the activation of TLR3 and TLR7/8. Finally, we assessed whether the virus-induced ECM was bioactive by measuring the amount of migration and proliferation of virus-naive cells that seeded onto the ECM. Basically, ECM from asthmatic ASM cells induced twofold greater migration of virus-naive ASM cells than ECM from nonasthmatic ASM cells, and these rates of migration were further increased on RV-modulated ECM. Increased migration on the RV-modulated ECM was not due to increased cell proliferation, as RV-modulated ECM decreased the proliferation of virus-naive cells. Our results suggest that viruses may contribute to airway remodeling through increased ECM deposition, which in turn may contribute to increased ASM mass via increased cell migration.

β-Catenin signaling is required for TGF-β1-induced extracellular matrix production by airway smooth muscle cells

2011 ◽  
Vol 301 (6) ◽  
pp. L956-L965 ◽  
Author(s):  
Hoeke A. Baarsma ◽  
Mark H. Menzen ◽  
Andrew J. Halayko ◽  
Herman Meurs ◽  
Huib A. M. Kerstjens ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Protein Expression ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Gene Transcription ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Luciferase Reporter ◽  
Airway Smooth Muscle Cells

Chronic inflammatory airway diseases like asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway remodeling with altered extracellular matrix (ECM) deposition. Transforming growth factor-β1 (TGF-β1) is upregulated in asthma and COPD and contributes to tissue remodeling in the airways by driving ECM production by structural cells, including airway smooth muscle. In this study, we investigated the activation of β-catenin signaling and its contribution to ECM production by airway smooth muscle cells in response to TGF-β1. Stimulation of airway smooth muscle cells with TGF-β1 resulted in a time-dependent increase of total and nonphosphorylated β-catenin protein expression via induction of β-catenin mRNA and inhibition of GSK-3. In addition, the TGF-β1-induced β-catenin activated TCF/LEF-dependent gene transcription, as determined by the β-catenin sensitive TOP-flash luciferase reporter assay. Furthermore, TGF-β1 stimulation increased mRNA expression of collagen Iα1, fibronectin, versican, and PAI-1. Pharmacological inhibition of β-catenin by PKF115-584 or downregulation of β-catenin expression by specific small interfering RNA (siRNA) substantially inhibited TGF-β1-induced expression of the ECM genes. Fibronectin protein deposition by airway smooth muscle cells in response to TGF-β1 was also inhibited by PKF115-584 and β-catenin siRNA. Moreover, transfection of airway smooth muscle cells with a nondegradable β-catenin mutant (S33Y β-catenin) was sufficient for inducing fibronectin protein expression. Collectively, these findings indicate that β-catenin signaling is activated in response to TGF-β1 in airway smooth muscle cells, which is required and sufficient for the regulation of ECM protein production. Targeting β-catenin-dependent gene transcription may therefore hold promise as a therapeutic intervention in airway remodeling in both asthma and COPD.

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.

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