scholarly journals NOX4-Derived ROS Promotes Collagen I Deposition in Bronchial Smooth Muscle Cells by Activating Noncanonical p38MAPK/Akt-Mediated TGF-β Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Binwei Hao ◽  
Ruiting Sun ◽  
Xiaotong Guo ◽  
Lili Zhang ◽  
Jieda Cui ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Differentiation ◽  
Akt Signaling ◽  
Collagen I ◽  
Control Group ◽  
Ros Production ◽  
Bronchial Smooth Muscle ◽  
Copd Patients ◽  
Bronchial Smooth Muscle Cells ◽  
Tgf Β1

Background. Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD). NADPH oxidase 4- (NOX4-) mediated reactive oxygen species (ROS) production plays a crucial role in cell differentiation and extracellular matrix (ECM) synthesis in ASM remodeling. However, the precise mechanisms underpinning its pathogenic roles remain elusive. Methods. The expression of NOX4 and TGF-β1 in the airway of the lung was measured in COPD patients and the control group. Cigarette smoke- (CS-) induced emphysema mice were generated, and the alteration of α-SMA, NOX4, TGF-β1, and collagen I was accessed. The changes of the expression of ECM markers, NOX4, components of TGF-β/Smad, and MAPK/Akt signaling in human bronchial smooth muscle cells (HBSMCs) were ascertained for delineating mechanisms of NOX4-mediated ROS production on cell differentiation and remodeling in human ASM cells. Results. An increased abundance of NOX4 and TGF-β1 proteins in the epithelial cells and ASM of lung was observed in COPD patients compared with the control group. Additionally, an increased abundance expression of NOX4 and α-SMA was observed in the lungs of the CS-induced emphysema mouse model. TGF-β1 displayed abilities to increase the oxidative burden and collagen I production, along with enhanced phosphorylation of ERK, p38MAPK, and p-Akt473 in HBSMCs. These effects of TGF-β1 could be inhibited by the ROS scavenger N-acetylcysteine (NAC), siRNA-mediated knockdown of Smad3 and NOX4, and pharmacological inhibitors SB203580 (p38MAPK inhibitor) and LY294002 (Akt inhibitor). Conclusions. NOX4-mediated ROS production alters TGF-β1-induced cell differentiation and collagen I protein synthesis in HBSMCs in part through the p38MAPK/Akt signaling pathway in a Smad-dependent manner.

Down-regulation of miR-140-3p is a cause of the interlukin-13-induced up-regulation of RhoA protein in bronchial smooth muscle cells

Small GTPases ◽  
2021 ◽  
pp. 1-6
Author(s):  
Yoshihiko Chiba ◽  
Yusuke Ando ◽  
Yasuna Kato ◽  
Motohiko Hanazaki ◽  
Hiroyasu Sakai
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Down Regulation ◽  
Bronchial Smooth Muscle ◽  
Rhoa Protein ◽  
Bronchial Smooth Muscle Cells

scholarly journals Endothelin generating pathway through endothelin1-31 in human cultured bronchial smooth muscle cells

1999 ◽  
Vol 127 (6) ◽  
pp. 1415-1421 ◽  
Author(s):  
Yoko Hayasaki-Kajiwara ◽  
Noriyuki Naya ◽  
Toshitake Shimamura ◽  
Takanori Iwasaki ◽  
Masatoshi Nakajima
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Bronchial Smooth Muscle ◽  
Bronchial Smooth Muscle Cells

scholarly journals Functional KCa3.1 Channels Regulate Steroid Insensitivity in Bronchial Smooth Muscle Cells

2013 ◽  
Vol 191 (5) ◽  
pp. 2624-2636 ◽  
Author(s):  
Latifa Chachi ◽  
Aarti Shikotra ◽  
S. Mark Duffy ◽  
Omar Tliba ◽  
Christopher Brightling ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Bronchial Smooth Muscle ◽  
Bronchial Smooth Muscle Cells

scholarly journals Rhinovirus and dsRNA Induce RIG-I-Like Receptors and Expression of Interferon β and λ1 in Human Bronchial Smooth Muscle Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e62718 ◽  
Author(s):  
Jenny Calvén ◽  
Yuliana Yudina ◽  
Lena Uller
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Interferon Β ◽  
Bronchial Smooth Muscle ◽  
Bronchial Smooth Muscle Cells

scholarly journals TLR3/TAK1 signalling regulates rhinovirus-induced interleukin-33 in bronchial smooth muscle cells

2020 ◽  
Vol 6 (4) ◽  
pp. 00147-2020
Author(s):  
Sangeetha Ramu ◽  
Jenny Calvén ◽  
Charalambos Michaeloudes ◽  
Mandy Menzel ◽  
Hamid Akbarshahi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Severe Asthma ◽  
Poly I:C ◽  
Healthy Controls ◽  
Bronchial Smooth Muscle ◽  
Interleukin 33 ◽  
Asthma Exacerbations ◽  
Gene And Protein Expression ◽  
Bronchial Smooth Muscle Cells

BackgroundAsthma exacerbations are commonly associated with rhinovirus (RV) infection. Interleukin-33 (IL-33) plays an important role during exacerbation by enhancing Type 2 inflammation. Recently we showed that RV infects bronchial smooth muscle cells (BSMCs) triggering production of interferons and IL-33. Here we compared levels of RV-induced IL-33 in BSMCs from healthy and asthmatic subjects, and explored the involvement of pattern-recognition receptors (PRRs) and downstream signalling pathways in IL-33 expression.MethodBSMCs from healthy and severe and non-severe asthmatic patients were infected with RV1B or stimulated with the PRR agonists poly(I:C) (Toll-like receptor 3 (TLR3)), imiquimod (TLR7) and poly(I:C)/LyoVec (retinoic acid-inducible gene 1 (RIG-I)/melanoma differentiation-associated protein 5 (MDA5)). Knockdown of TLR3, RIG-I and MDA5 was performed, and inhibitors targeting TBK1, nuclear factor-κB (NF-κB) and transforming growth factor (TGF)-β-activated kinase 1 (TAK1) were used. Gene and protein expression were assessed.ResultsRV triggered IL-33 gene and protein expression in BSMCs. BSMCs from patients with non-severe asthma showed higher baseline and RV-induced IL-33 gene expression compared to cells from patients with severe asthma and healthy controls. Furthermore, RV-induced IL-33 expression in BSMCs from healthy and asthmatic individuals was attenuated by knockdown of TLR3. Inhibition of TAK1, but not NF-κB or TBK1, limited RV-induced IL-33. The cytokine secretion profile showed higher production of IL-33 in BSMCs from patients with non-severe asthma compared to healthy controls upon RV infection. In addition, BSMCs from patients with non-severe asthma had higher levels of RV-induced IL-8, TNF-α, IL-1β, IL-17A, IL-5 and IL-13.ConclusionRV infection caused higher levels of IL-33 and increased pro-inflammatory and Type 2 cytokine release in BSMCs from patients with non-severe asthma. RV-induced IL-33 expression was mainly regulated by TLR3 and downstream via TAK1. These signalling molecules represent potential therapeutic targets for treating asthma exacerbations.

Membrane currents in canine bronchial artery and their regulation by excitatory agonists

2002 ◽  
Vol 282 (6) ◽  
pp. L1358-L1365 ◽  
Author(s):  
Q. J. Li ◽  
L. J. Janssen
Keyword(s):  
Smooth Muscle ◽  
Bronchial Artery ◽  
Similar Degree ◽  
Ion Currents ◽  
Significant Suppression ◽  
Bronchial Smooth Muscle ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Bronchial Smooth Muscle Cells ◽  
Airway Physiology

The bronchial vasculature plays an important role in airway physiology and pathophysiology. We investigated the ion currents in canine bronchial smooth muscle cells using patch-clamp techniques. Sustained outward K+current evoked by step depolarizations was significantly inhibited by tetraethylamonium (1 and 10 mM) or by charybdotoxin (10−6M) but was not significantly affected by 4-aminopyridine (1 or 5 mM), suggesting that it was primarily a Ca2+-activated K+current. Consistent with this, the K+current was markedly increased by raising external Ca2+to 4 mM but was decreased by nifedipine (10−6M) or by removing external Ca2+. When K+currents were blocked (by Cs+in the pipette), step depolarizations evoked transient inward currents with characteristics of L-type Ca2+current as follows: 1) activation that was voltage dependent (threshold and maximal at −50 and −10 mV, respectively); 2) inactivation that was time dependent and voltage dependent (voltage causing 50% maximal inactivation of −26 ± 22 mV); and 3) blockade by nifedipine (10−6M). The thromboxane mimetic U-46619 (10−6M) caused a marked augmentation of outward K+current (as did 10 mM caffeine) lasting only 10–20 s; this was followed by significant suppression of the K+current lasting several minutes. Phenylephrine (10−4M) also suppressed the K+current to a similar degree but did not cause the initial transient augmentation. None of these three agonists elicited inward current of any kind. We conclude that bronchial arterial smooth muscle expresses Ca2+-dependent K+channels and voltage-dependent Ca2+channels and that its excitation does not involve activation of Cl−channels.

Double-stranded RNA-induced CC chemokine synthesis in human bronchial smooth muscle cells and toll-like receptor 3

2005 ◽  
Vol 115 (2) ◽  
pp. S270
Author(s):  
K. Niimi ◽  
K. Asano ◽  
Y. Shiraishi ◽  
M. Wakaki ◽  
T. Nakajima ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Toll Like Receptor ◽  
Bronchial Smooth Muscle ◽  
Double Stranded Rna ◽  
Cc Chemokine ◽  
Bronchial Smooth Muscle Cells
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