Airway Smooth Muscle and Asthma

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 29186

Special Issue Editors


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Guest Editor
Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA
Interests: cytoskeletal regulation of smooth muscle functions; pathogenesis of asthma and hypertension

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Guest Editor
Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, New Brunswick, NJ 08091, USA
Interests: biophysics; airway smooth muscle; lung diseases
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Special Issue Information

Dear Colleagues,

Airway smooth muscle (ASM) plays a multifaceted role in the physiological functions of the lung. ASM contracts and shortens in response to a wide range of endogenous and exogenous signals; hence, it represents the pivotal cell regulating bronchomotor tone, airway caliber, and ventilation distribution. ASM also proliferates and migrates upon the alterations in external and internal environments, which are critical for lung development and tissue homeostasis. In addition, ASM is capable of producing and secreting bioactive molecules, such as cytokines and matrix proteins, that affect the functions of other structural cells in the airways.

It has been long believed that dysfunction of ASM contraction, proliferation, and immunomodulation contributes to the pathophysiology of asthma, by inducing airway hyperresponsiveness, airway remodeling, and immune inflammatory responses in the airways. Despite the progress that has been achieved in ASM biology and asthma pathology in recent years, there are many unanswered questions in this research field, some of which include the following: What role does ASM play in asthma pathogenesis? How does ASM contribute to asthma progression? Does ASM have unexplored functions? How are the known functions of ASM regulated under physiological and pathological conditions? The aim of this Special Issue is to assemble original research and reviews describing new developments in ASM biology and asthma pathogenesis. We hope that the contributions from these laboratories will be beneficial for researchers with a particular interest in physiological functions of the lung, and those aiming to delve into this fascinating field of basic sciences and translational medicine.

Prof. Dr. Dale D. Tang
Prof. Dr. Steven S. An
Guest Editors

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Keywords

  • airway smooth muscle
  • asthma
  • contraction
  • proliferation
  • migration

Published Papers (8 papers)

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Editorial

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3 pages, 180 KiB  
Editorial
Airway Smooth Muscle and Asthma
by Steven An and Dale D. Tang
Cells 2023, 12(6), 882; https://doi.org/10.3390/cells12060882 - 12 Mar 2023
Cited by 1 | Viewed by 1316
Abstract
Airway smooth muscle (ASM) was first described in 1804 by Franz Daniel Reisseisen (as related by Otis (1983)) [...] Full article
(This article belongs to the Special Issue Airway Smooth Muscle and Asthma)

Research

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8 pages, 1642 KiB  
Communication
The Bronchoprotective Effects of Dual Pharmacology, Muscarinic Receptor Antagonist and β2 Adrenergic Receptor Agonist Navafenterol in Human Small Airways
by Joseph Antony Jude, Ian Dainty, Nikhil Karmacharya, William Jester and Reynold Panettieri
Cells 2023, 12(2), 240; https://doi.org/10.3390/cells12020240 - 6 Jan 2023
Cited by 4 | Viewed by 1652
Abstract
Bronchodilators and anti-inflammatory agents are the mainstream treatments in chronic obstructive and pulmonary disease (COPD) and asthma. The combination of β2 adrenergic receptor (β2AR) agonists and muscarinic antagonists shows superior bronchoprotective effects compared to these agents individually. Navafenterol (AZD8871) is [...] Read more.
Bronchodilators and anti-inflammatory agents are the mainstream treatments in chronic obstructive and pulmonary disease (COPD) and asthma. The combination of β2 adrenergic receptor (β2AR) agonists and muscarinic antagonists shows superior bronchoprotective effects compared to these agents individually. Navafenterol (AZD8871) is a single-molecule, dual pharmacology agent combining muscarinic antagonist and β2AR agonist functions, currently in development as a COPD therapeutic. In precision-cut human lung slices (hPCLS), we investigated the bronchoprotective effect of navafenterol against two non-muscarinic contractile agonists, histamine and thromboxane A2 (TxA2) analog (U46619). Navafenterol pre-treatment significantly attenuated histamine-induced bronchoconstriction and β2AR antagonist propranolol reversed this inhibitory effect. TxA2 analog-induced bronchoconstriction was attenuated by navafenterol pre-treatment, albeit to a lesser magnitude than that of histamine-induced bronchoconstriction. Propranolol completely reversed the inhibitory effect of navafenterol on TxA2 analog-induced bronchoconstriction. In the presence of histamine or TxA2 analog, navafenterol exhibits bronchoprotective effect in human airways and it is primarily mediated by β2AR agonism of navafenterol. Full article
(This article belongs to the Special Issue Airway Smooth Muscle and Asthma)
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18 pages, 1994 KiB  
Article
IL-5 and GM-CSF, but Not IL-3, Promote the Proliferative Properties of Inflammatory-like and Lung Resident-like Eosinophils in the Blood of Asthma Patients
by Jolita Palacionyte, Andrius Januskevicius, Egle Vasyle, Airidas Rimkunas, Ieva Bajoriuniene, Skaidrius Miliauskas and Kestutis Malakauskas
Cells 2022, 11(23), 3804; https://doi.org/10.3390/cells11233804 - 28 Nov 2022
Cited by 4 | Viewed by 1867
Abstract
Blood eosinophils can be described as inflammatory-like (iEOS-like) and lung-resident-like (rEOS-like) eosinophils. This study is based on the hypothesis that eosinophilopoetins such as interleukin (IL)-3 and IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) alter the proliferative properties of eosinophil subtypes and may be associated [...] Read more.
Blood eosinophils can be described as inflammatory-like (iEOS-like) and lung-resident-like (rEOS-like) eosinophils. This study is based on the hypothesis that eosinophilopoetins such as interleukin (IL)-3 and IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) alter the proliferative properties of eosinophil subtypes and may be associated with the expression of their receptors on eosinophils. We investigated 8 individuals with severe nonallergic eosinophilic asthma (SNEA), 17 nonsevere allergic asthma (AA), and 11 healthy subjects (HS). For AA patients, a bronchial allergen challenge with Dermatophagoides pteronyssinus was performed. Eosinophils were isolated from peripheral blood using high-density centrifugation and magnetic separation methods. The subtyping of eosinophils was based on magnetic bead-conjugated antibodies against L-selectin. Preactivation by eosinophilopoetins was performed by incubating eosinophil subtypes with IL-3, IL-5, and GM-CSF, and individual combined cell cultures were prepared with airway smooth muscle (ASM) cells. ASM cell proliferation was assessed using an Alamar blue assay. The gene expression of eosinophilopoetin receptors was analyzed with a qPCR. IL-5 and GM-CSF significantly enhanced the proliferative properties of iEOS-like and rEOS-like cells on ASM cells in both SNEA and AA groups compared with eosinophils not activated by cytokines (p < 0.05). Moreover, rEOS-like cells demonstrated a higher gene expression of the IL-3 and IL-5 receptors compared with iEOS-like cells in the SNEA and AA groups (p < 0.05). In conclusion: IL-5 and GM-CSF promote the proliferative properties of iEOS-like and rEOS-like eosinophils; however, the effect of only IL-5 may be related to the expression of its receptors in asthma patients. Full article
(This article belongs to the Special Issue Airway Smooth Muscle and Asthma)
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15 pages, 3366 KiB  
Article
Nestin Modulates Airway Smooth Muscle Cell Migration by Affecting Spatial Rearrangement of Vimentin Network and Focal Adhesion Assembly
by Ruping Wang, Sakeeb Khan, Guoning Liao, Yidi Wu and Dale D. Tang
Cells 2022, 11(19), 3047; https://doi.org/10.3390/cells11193047 - 29 Sep 2022
Cited by 5 | Viewed by 1872
Abstract
Airway smooth muscle cell migration plays a role in the progression of airway remodeling, a hallmark of allergic asthma. However, the mechanisms that regulate cell migration are not yet entirely understood. Nestin is a class VI intermediate filament protein that is involved in [...] Read more.
Airway smooth muscle cell migration plays a role in the progression of airway remodeling, a hallmark of allergic asthma. However, the mechanisms that regulate cell migration are not yet entirely understood. Nestin is a class VI intermediate filament protein that is involved in the proliferation/regeneration of neurons, cancer cells, and skeletal muscle. Its role in cell migration is not fully understood. Here, nestin knockdown (KD) inhibited the migration of human airway smooth muscle cells. Using confocal microscopy and the Imaris software, we found that nestin KD attenuated focal adhesion sizes during cell spreading. Moreover, polo-like kinase 1 (Plk1) and vimentin phosphorylation at Ser-56 have been previously shown to affect focal adhesion assembly. Here, nestin KD reduced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation), vimentin phosphorylation at Ser-56, the contacts of vimentin filaments to paxillin, and the morphology of focal adhesions. Moreover, the expression of vimentin phosphorylation-mimic mutant S56D (aspartic acid substitution at Ser-56) rescued the migration, vimentin reorganization, and focal adhesion size of nestin KD cells. Together, our results suggest that nestin promotes smooth muscle cell migration. Mechanistically, nestin regulates Plk1 phosphorylation, which mediates vimenitn phosphorylation, the connection of vimentin filaments with paxillin, and focal adhesion assembly. Full article
(This article belongs to the Special Issue Airway Smooth Muscle and Asthma)
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13 pages, 2646 KiB  
Article
Smooth Muscle Myosin Localizes at the Leading Edge and Regulates the Redistribution of Actin-regulatory Proteins during Migration
by Ruping Wang, Eylon Arbel and Dale D. Tang
Cells 2022, 11(15), 2334; https://doi.org/10.3390/cells11152334 - 29 Jul 2022
Cited by 1 | Viewed by 2209
Abstract
Airway smooth muscle cell migration plays an essential role in airway development, repair, and remodeling. Smooth muscle myosin II has been traditionally thought to localize in the cytoplasm solely and regulates cell migration by affecting stress fiber formation and focal adhesion assembly. In [...] Read more.
Airway smooth muscle cell migration plays an essential role in airway development, repair, and remodeling. Smooth muscle myosin II has been traditionally thought to localize in the cytoplasm solely and regulates cell migration by affecting stress fiber formation and focal adhesion assembly. In this study, we unexpectedly found that 20-kDa myosin light chain (MLC20) and myosin-11 (MYH11), important components of smooth muscle myosin, were present at the edge of lamellipodia. The knockdown of MLC20 or MYH11 attenuated the recruitment of c-Abl, cortactinProfilin-1 (Pfn-1), and Abi1 to the cell edge. Moreover, myosin light chain kinase (MLCK) colocalized with integrin β1 at the tip of protrusion. The inhibition of MLCK attenuated the recruitment of c-Abl, cortactin, Pfn-1, and Abi1 to the cell edge. Furthermore, MLCK localization at the leading edge was reduced by integrin β1 knockdown. Taken together, our results demonstrate that smooth muscle myosin localizes at the leading edge and orchestrates the recruitment of actin-regulatory proteins to the tip of lamellipodia. Mechanistically, integrin β1 recruits MLCK to the leading edge, which catalyzes MLC20 phosphorylation. Activated myosin regulates the recruitment of actin-regulatory proteins to the leading edge, and promotes lamellipodial formation and migration. Full article
(This article belongs to the Special Issue Airway Smooth Muscle and Asthma)
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Review

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20 pages, 3079 KiB  
Review
Purification of Myosin from Bovine Tracheal Smooth Muscle, Filament Formation and Endogenous Association of Its Regulatory Complex
by Lu Wang, Isabel J. Sobieszek, Chun Y. Seow and Apolinary Sobieszek
Cells 2023, 12(3), 514; https://doi.org/10.3390/cells12030514 - 3 Feb 2023
Viewed by 1743
Abstract
Dynamic regulation of myosin filaments is a crucial factor in the ability of airway smooth muscle (ASM) to adapt to a wide length range. Increased stability or robustness of myosin filaments may play a role in the pathophysiology of asthmatic airways. Biochemical techniques [...] Read more.
Dynamic regulation of myosin filaments is a crucial factor in the ability of airway smooth muscle (ASM) to adapt to a wide length range. Increased stability or robustness of myosin filaments may play a role in the pathophysiology of asthmatic airways. Biochemical techniques for the purification of myosin and associated regulatory proteins could help elucidate potential alterations in myosin filament properties of asthmatic ASM. An effective myosin purification approach was originally developed for chicken gizzard smooth muscle myosin. More recently, we successfully adapted the procedure to bovine tracheal smooth muscle. This method yields purified myosin with or without the endogenous regulatory complex of myosin light chain kinase and myosin light chain phosphatase. The tight association of the regulatory complex with the assembled myosin filaments can be valuable in functional experiments. The purification protocol discussed here allows for enzymatic comparisons of myosin regulatory proteins. Furthermore, we detail the methodology for quantification and removal of the co-purified regulatory enzymes as a tool for exploring potentially altered phenotypes of the contractile apparatus in diseases such as asthma. Full article
(This article belongs to the Special Issue Airway Smooth Muscle and Asthma)
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17 pages, 1325 KiB  
Review
Current Understanding of Asthma Pathogenesis and Biomarkers
by Nazia Habib, Muhammad Asghar Pasha and Dale D. Tang
Cells 2022, 11(17), 2764; https://doi.org/10.3390/cells11172764 - 5 Sep 2022
Cited by 67 | Viewed by 13968
Abstract
Asthma is a heterogeneous lung disease with variable phenotypes (clinical presentations) and distinctive endotypes (mechanisms). Over the last decade, considerable efforts have been made to dissect the cellular and molecular mechanisms of asthma. Aberrant T helper type 2 (Th2) inflammation is the most [...] Read more.
Asthma is a heterogeneous lung disease with variable phenotypes (clinical presentations) and distinctive endotypes (mechanisms). Over the last decade, considerable efforts have been made to dissect the cellular and molecular mechanisms of asthma. Aberrant T helper type 2 (Th2) inflammation is the most important pathological process for asthma, which is mediated by Th2 cytokines, such as interleukin (IL)-5, IL-4, and IL-13. Approximately 50% of mild-to-moderate asthma and a large portion of severe asthma is induced by Th2-dependent inflammation. Th2-low asthma can be mediated by non-Th2 cytokines, including IL-17 and tumor necrosis factor-α. There is emerging evidence to demonstrate that inflammation-independent processes also contribute to asthma pathogenesis. Protein kinases, adapter protein, microRNAs, ORMDL3, and gasdermin B are newly identified molecules that drive asthma progression, independent of inflammation. Eosinophils, IgE, fractional exhaled nitric oxide, and periostin are practical biomarkers for Th2-high asthma. Sputum neutrophils are easily used to diagnose Th2-low asthma. Despite progress, more studies are needed to delineate complex endotypes of asthma and to identify new and practical biomarkers for better diagnosis, classification, and treatment. Full article
(This article belongs to the Special Issue Airway Smooth Muscle and Asthma)
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23 pages, 1952 KiB  
Review
Sex Steroids Effects on Asthma: A Network Perspective of Immune and Airway Cells
by Niyati A. Borkar, Colin Kelly Combs and Venkatachalem Sathish
Cells 2022, 11(14), 2238; https://doi.org/10.3390/cells11142238 - 19 Jul 2022
Cited by 12 | Viewed by 3448
Abstract
A multitude of evidence has suggested the differential incidence, prevalence and severity of asthma between males and females. A compilation of recent literature recognized sex differences as a significant non-modifiable risk factor in asthma pathogenesis. Understanding the cellular and mechanistic basis of sex [...] Read more.
A multitude of evidence has suggested the differential incidence, prevalence and severity of asthma between males and females. A compilation of recent literature recognized sex differences as a significant non-modifiable risk factor in asthma pathogenesis. Understanding the cellular and mechanistic basis of sex differences remains complex and the pivotal point of this ever elusive quest, which remains to be clarified in the current scenario. Sex steroids are an integral part of human development and evolution while also playing a critical role in the conditioning of the immune system and thereby influencing the function of peripheral organs. Classical perspectives suggest a pre-defined effect of sex steroids, generalizing estrogens popularly under the “estrogen paradox” due to conflicting reports associating estrogen with a pro- and anti-inflammatory role. On the other hand, androgens are classified as “anti-inflammatory,” serving a protective role in mitigating inflammation. Although considered mainstream and simplistic, this observation remains valid for numerous reasons, as elaborated in the current review. Women appear immune-favored with stronger and more responsive immune elements than men. However, the remarkable female predominance of diverse autoimmune and allergic diseases contradicts this observation suggesting that hormonal differences between the sexes might modulate the normal and dysfunctional regulation of the immune system. This review illustrates the potential relationship between key elements of the immune cell system and their interplay with sex steroids, relevant to structural cells in the pathophysiology of asthma and many other lung diseases. Here, we discuss established and emerging paradigms in the clarification of observed sex differences in asthma in the context of the immune system, which will deepen our understanding of asthma etiopathology. Full article
(This article belongs to the Special Issue Airway Smooth Muscle and Asthma)
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