145
Views
0
CrossRef citations to date
0
Altmetric
Review

Airway smooth muscle in contractility and remodeling of asthma: potential drug target mechanisms

&
Pages 19-29 | Received 30 Sep 2022, Accepted 03 Feb 2023, Published online: 13 Feb 2023

References

  • McIvor A, Kaplan A. A call to action for improving clinical outcomes in patients with asthma. NPJ Prim Care Respir Med. 2020;30(1):1–5.
  • Nunes C, Pereira AM, Morais-Almeida M. Asthma costs and social impact. Asthma Res Pract. 2017;3(1):1–11.
  • Diver S, Russell R, Brightling C. New and emerging drug treatments for severe asthma. Clin Exp Allergy. 2018;48(3):241–252.
  • Prakash Y. Asthma without borders. American Physiological Society Bethesda. 2020;MD:L1001–L1003.
  • King GG, James A, Harkness L, et al. Pathophysiology of severe asthma: we’ve only just started. Respirology. 2018;23(3):262–271
  • Kudo M, Ishigatsubo Y, Aoki I. Pathology of asthma. Front Microbiol. 2013;4:263.
  • Holgate ST, Holloway J, Wilson S, et al. Understanding the pathophysiology of severe asthma to generate new therapeutic opportunities. J Allergy Clin Immunol. 2006;117(3):496–506
  • Prakash Y. Airway smooth muscle in airway reactivity and remodeling: what have we learned? Am J Physiol Lung Cell Mol Physiol. 2013;305(12):L912–L933.
  • Wardlaw A, Brightling C, Green R, et al. New insights into the relationship between airway inflammation and asthma. Clin Sci. 2002;103(2):201–211
  • Agache I, Akdis C, Jutel M, et al. Untangling asthma phenotypes and endotypes. Allergy. 2012;67(7):835–846
  • Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16(1):45–56.
  • Zhu M-S. A “bitter” end to asthma revealed. Protein Cell. 2011;2(6):433.
  • Prakash Y, Sathish V, Thompson MA, et al. Asthma and sarcoplasmic reticulum Ca2+ reuptake in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2009;297(4):L794–L794
  • Bergantin LB. The interplay between asthma and other diseases: role of Ca2+/cAMP Signalling. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune. Endocrine & Metabolic Disorders). 2020;20(3):321–327.
  • Sivaraman V, Onyenwoke RU. Calcium Signaling Derangement and Disease Development and Progression. MDPI. 2021;291
  • Baarsma HA, Han B, Poppinga WJ, et al. Disruption of AKAP-PKA Interaction Induces Hypercontractility With Concomitant Increase in Proliferation Markers in Human Airway Smooth Muscle. Front Cell Dev Biol. 2020;8:165.
  • Britt JRD, Thompson MA, Freeman MR, et al. Vitamin D reduces inflammation-induced contractility and remodeling of asthmatic human airway smooth muscle. Ann Am Thorac Soc. 2016;13(Supplement 1):S97–S98
  • Parikh P, Britt JRD, Manlove LJ, et al. Hyperoxia-induced cellular senescence in fetal airway smooth muscle cells. Am J Respir Cell Mol Biol. 2019;61(1):51–60
  • Mazzarella G, Bianco A, Catena E, et al. Th1/Th2 lymphocyte polarization in asthma. Allergy. 2000;55:6–9.
  • León B, Ballesteros-Tato A. Modulating Th2 cell immunity for the treatment of asthma. Front Immunol. 2021;12:637948.
  • Chiu C-J, Huang M-T. Asthma in the precision medicine era: biologics and probiotics. Int J Mol Sci. 2021;22(9):4528.
  • Barnig C, Frossard N, Levy BD. Towards targeting resolution pathways of airway inflammation in asthma. Pharmacol Ther. 2018;186:98–113.
  • Busse WW, Rosenwasser LJ. Mechanisms of asthma. J Allergy Clin Immunol. 2003;111(3):S799–S804.
  • Lemanske JRF, Busse WW. Asthma: clinical expression and molecular mechanisms. J Allergy Clin Immunol. 2010;125(2):S95–S102.
  • Murdoch JR, Lloyd CM. Chronic inflammation and asthma. Mutat Res. 2010;690(1–2):24–39.
  • Coverstone AM, Seibold MA, Peters MC. Diagnosis and management of T2-high asthma. J Allergy Clin Immunol. 2020;8(2):442–450.
  • Poulsen LK, Hummelshoj L. Triggers of IgE class switching and allergy development. Ann Med. 2007;39(6):440–456.
  • Steinke JW, Borish L. Th2 cytokines and asthma—Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res. 2001;2(2):1–5.
  • Fulkerson PC, Schollaert KL, Bouffi C, et al. IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation. J Immunol. 2014;193(8):4043–4052
  • Roufosse F. Targeting the interleukin-5 pathway for treatment of eosinophilic conditions other than asthma. frontiers in Medicine. 2018;5:49.
  • Chakraborty S, Kubatzky KF, Mitra DK. An update on interleukin-9: from its cellular source and signal transduction to its role in immunopathogenesis. Int J Mol Sci. 2019;20(9):2113.
  • Soussi-Gounni A, Kontolemos M, Hamid Q. Role of IL-9 in the pathophysiology of allergic diseases. J Allergy Clin Immunol. 2001;107(4):575–582.
  • Ingram JL, Kraft M. IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies. J Allergy Clin Immunol. 2012;130(4):829–842.
  • Smelter D, Thompson M, Meuchel L, et al. Thymic Stromal Lymphopoietin (TSLP) and Airway Smooth Muscle. FASEB J. 2009;23:622.6–622.6.
  • Lloyd CM, Hessel EM. Functions of T cells in asthma: more than just TH2 cells. Nat Rev Immunol. 2010;10(12):838–848.
  • Smelter DF, Sathish V, Thompson MA, et al. Thymic stromal lymphopoietin in cigarette smoke-exposed human airway smooth muscle. J Immunol. 2010;185(5):3035–3040
  • Diver S, Khalfaoui L, Emson C, et al. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9(11):1299–1312.
  • Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015;517(7534):293–301.
  • Bartemes KR, Kephart GM, Fox SJ, et al. Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol. 2014;134(3):671–678. e4
  • Chen R, Smith SG, Salter B, et al. Allergen-induced increases in sputum levels of group 2 innate lymphoid cells in subjects with asthma. Am J Respir Crit Care Med. 2017;196(6):700–712.
  • Nakagome K, Nagata M. Innate immune responses by respiratory viruses, including rhinovirus, during asthma exacerbation. Front Immunol. 2022;13:865973.
  • Shen X, Pasha MA, Hidde K, et al. Group 2 innate lymphoid cells promote airway hyperresponsiveness through production of VEGFA. J Allergy Clin Immunol. 2018;141(5):1929–1931.
  • Fitzpatrick AM, Moore WC. Severe asthma phenotypes—how should they guide evaluation and treatment? J Allergy Clin Immunol. 2017;5(4):901–908.
  • McGrath KW, Icitovic N, Boushey HA, et al. A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med. 2012;185(6):612–619.
  • Doe C, Bafadhel M, Siddiqui S, et al. Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. Chest. 2010;138(5):1140–1147.
  • Al-Ramli W, Préfontaine D, Chouiali F, et al. TH17-associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol. 2009;123(5):1185–1187.
  • Peters MC, Ringel L, Dyjack N, et al. A transcriptomic method to determine airway immune dysfunction in T2-high and T2-low asthma. Am J Respir Crit Care Med. 2019;199(4):465–477.
  • Kuo C-HS, Pavlidis S, Loza M, et al. T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED. Eur Respir J. 2017;49(2):1602135.
  • Prakash Y, Thompson MA, Pabelick CM. Brain-derived neurotrophic factor in TNF-α modulation of Ca2+ in human airway smooth muscle. Am J Respir Cell Mol Biol. 2009;41(5):603–611.
  • Kips JC, Tavernier J, Pauwels RA. Tumor Necrosis Factor Causes Bronchial Hyperresponsiveness in Rats. Am Rev Respir Dis. 1992;145:332–336.
  • Amrani Y, Chen H, Panettieri RA. Activation of tumor necrosis factor receptor 1 in airway smooth muscle: a potential pathway that modulates bronchial hyper-responsiveness in asthma? Respir Res. 2000;1(1):49–53.
  • Prakash Y, Iyanoye A, Ay B, et al. Neurotrophin effects on intracellular Ca2+ and force in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2006;291(3):L447–L456.
  • Prakash Y. Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease. Am J Physiol Lung Cell Mol Physiol. 2016;311(6):L1113–L1140.
  • Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern med review. 2003;8(3):223–246.
  • Britt JRD, Thompson MA, Sasse S, et al. Th1 cytokines TNF-α and IFN-γ promote corticosteroid resistance in developing human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2019;316(1):L71–L81.
  • Tliba O, Damera G, Banerjee A, et al. Cytokines induce an early steroid resistance in airway smooth muscle cells: novel role of interferon regulatory factor-1. Am J Respir Cell Mol Biol. 2008;38(4):463–472.
  • Vignola AM, Mirabella F, Costanzo G, et al. Airway remodeling in asthma. Chest. 2003;123(3):417S–422S.
  • Barnes PJ, Drazen JM. Asthma and COPD. 2002; pp. 343–359.
  • Berair R, Brightling CE. Asthma therapy and its effect on airway remodelling. Drugs. 2014;74(12):1345–1369.
  • Grainge CL, Lau LC, Ward JA, et al. Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med. 2011;364(21):2006–2015.
  • Swartz M, Tschumperlin D, Kamm R, et al. Mechanical stress is communicated between different cell types to elicit matrix remodeling. Proc Natl Acad Sci U S A. 2001;98(11):6180–6185.
  • Liesker JJ, Ten Hacken NH, Zeinstra-Smith M, et al. Reticular basement membrane in asthma and COPD: similar thickness, yet different composition. Int J Chron Obstruct Pulmon Dis. 2009;4:127.
  • Chakir J, Shannon J, Molet S, et al. Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression. J Allergy Clin Immunol. 2003;111(6):1293–1298.
  • Mostaço-Guidolin LB, Osei ET, Ullah J, et al. Defective fibrillar collagen organization by fibroblasts contributes to airway remodeling in asthma. Am J Respir Crit Care Med. 2019;200(4):431–443.
  • Niimi A, Matsumoto H, Takemura M, et al. Relationship of airway wall thickness to airway sensitivity and airway reactivity in asthma. Am J Respir Crit Care Med. 2003;168(8):983–988.
  • Hendrix AY, Kheradmand F. The role of matrix metalloproteinases in development, repair, and destruction of the lungs. Prog Mol Biol Transl Sci. 2017;148:1–29.
  • Sacco O, Silvestri M, Sabatini F, et al. Epithelial cells and fibroblasts: structural repair and remodelling in the airways. Paediatr Respir Rev. 2004;5:S35–S40.
  • Freeman MR, Sathish V, Manlove L, et al. Brain-derived neurotrophic factor and airway fibrosis in asthma. Am J Physiol Lung Cell Mol Physiol. 2017;313(2):L360–L370.
  • Janulaityte I, Januskevicius A, Kalinauskaite-Zukauske V, et al. In Vivo Allergen-Activated Eosinophils Promote Collagen I and Fibronectin Gene Expression in Airway Smooth Muscle Cells via TGF-β 1 Signaling Pathway in Asthma. Int J Mol Sci. 2020;21(5):1837
  • Royce SG, Cheng V, Samuel CS, et al. The regulation of fibrosis in airway remodeling in asthma. Mol Cell Endocrinol. 2012;351(2):167–175
  • Prakash Y, Martin RJ. Brain-derived neurotrophic factor in the airways. Pharmacol Ther. 2014;143(1):74–86.
  • Ambhore NS, Kalidhindi RSR, Loganathan J, et al. Role of differential estrogen receptor activation in airway hyperreactivity and remodeling in a murine model of asthma. Am J Respir Cell Mol Biol. 2019;61(4):469–480
  • Benayoun L, Druilhe A, Dombret M-C, et al. Airway structural alterations selectively associated with severe asthma. Am J Respir Crit Care Med. 2003;167(10):1360–1368
  • Woodruff PG, Dolganov GM, Ferrando RE, et al. Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression. Am J Respir Crit Care Med. 2004;169(9):1001–1006
  • Ijpma G, Panariti A, Lauzon A-M, et al. Directional preference of airway smooth muscle mass increase in human asthmatic airways. Am J Physiol Lung Cell Mol Physiol. 2017;312(6):L845–L854
  • Heijink IH, Postma DS, Noordhoek JA, et al. House dust mite–promoted epithelial-to-mesenchymal transition in human bronchial epithelium. Am J Respir Cell Mol Biol. 2010;42(1):69–79
  • Torrego A, Hew M, Oates T, et al. Expression and activation of TGF-β isoforms in acute allergen-induced remodelling in asthma. Thorax. 2007;62(4):307–313
  • Woodman L, Siddiqui S, Cruse G, et al. Mast cells promote airway smooth muscle cell differentiation via autocrine up-regulation of TGF-β1. J Immunol. 2008;181(7):5001–5007
  • Juncadella IJ, Kadl A, Sharma AK, et al. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature. 2013;493(7433):547–551
  • Bonser LR, Erle DJ. Airway mucus and asthma: the role of MUC5AC and MUC5B. J Clin Med. 2017;6(12):112.
  • Saglani S, Lloyd CM. Novel concepts in airway inflammation and remodelling in asthma. Eur Respir J. 2015;46(6):1796–1804.
  • Milanese M, Crimi E, Scordamaglia A, et al. On the functional consequences of bronchial basement membrane thickening. J Appl Physiol. 2001;91(3):1035–1040
  • Kasahara K, Shiba K, Ozawa T, et al. Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma. Thorax. 2002;57(3):242–246
  • Shiba K, Kasahara K, Nakajima H, et al. Structural changes of the airway wall impair respiratory function, even in mild asthma. Chest. 2002;122(5):1622–1626
  • Salvato G. Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects. Thorax. 2001;56(12):902–906.
  • Pałgan K, Bartuzi Z. Angiogenesis in bronchial asthma. Int J Immunopathol Pharmacol. 2015;28(3):415–420.
  • Kistemaker LE, Gosens R. Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling. Trends Pharmacol Sci. 2015;36(3):164–171.
  • Haag S, Matthiesen S, Juergens U, et al. Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts. Eur Respir J. 2008;32(3):555–562.
  • Oenema TA, Mensink G, Smedinga L, et al. Cross-talk between transforming growth factor–β1 and muscarinic M2 receptors augments airway smooth muscle proliferation. Am J Respir Cell Mol Biol. 2013;49(1):18–27.
  • Borak J, Lefkowitz R. Bronchial hyperresponsiveness. Occup Med. 2016;66(2):95–105.
  • Brannan JD, Lougheed MD. Airway hyperresponsiveness in asthma: mechanisms, clinical significance, and treatment. Front Physiol. 2012;3:460.
  • Crapo R. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000;161:309–329.
  • Slats AM, Janssen K, Van Schadewijk A, et al. Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma. J Allergy Clin Immunol. 2008;121(5):1196–1202.
  • Boulet L-P. Airway remodeling in asthma: update on mechanisms and therapeutic approaches. Curr Opin Pulm Med. 2018;24(1):56–62.
  • Lam M, Lamanna E, Bourke JE. Regulation of airway smooth muscle contraction in health and disease. Smooth Muscle Spontaneous Activity. 2019;1124:381–422
  • Camoretti-Mercado B, Lockey RF. Airway smooth muscle pathophysiology in asthma. J Allergy Clin Immunol. 2021;147(6):1983–1995.
  • Sieck GC, White TA, Thompson MA, et al. Regulation of store-operated Ca2+ entry by CD38 in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2008;294(2):L378–L385.
  • Li G, Cohen JA, Martines C, et al. Preserving airway smooth muscle contraction in precision-cut lung slices. Sci Rep. 2020;10(1):1–9.
  • Álvarez-Santos MD, Álvarez-González M, Estrada-Soto S, et al. Regulation of myosin light-chain phosphatase activity to generate airway smooth muscle hypercontractility. Front Physiol. 2020;11:701.
  • Prakash Y, Thompson MA, Vaa B, et al. Caveolins and intracellular calcium regulation in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2007;293(5):L1118–L1126.
  • Sathish V, Thompson MA, Bailey JP, et al. Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+ reuptake in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2009;297(1):L26–L34.
  • Trian T, Benard G, Begueret H, et al. Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma. J Exp Med. 2007;204(13):3173–3181.
  • Jude JA, Wylam ME, Walseth TF, et al. Calcium signaling in airway smooth muscle. Proceedings of the American Thoracic Society. 2008;5(1):15–22.
  • Sanderson MJ, Delmotte P, Bai Y, et al. Regulation of airway smooth muscle cell contractility by Ca2+ signaling and sensitivity. Proceedings of the American Thoracic Society. 2008;5(1):23–31.
  • Smith P, Tokui T, Ikebe M. Mechanical strain increases contractile enzyme activity in cultured airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 1995;268(6):L999–L1005.
  • Puetz S, Lubomirov LT, Pfitzer G. Regulation of smooth muscle contraction by small GTPases. Physiology. 2009;24(6):342–356.
  • Chiba T, Nakahara T, Hashimoto‐Hachiya A, et al. The leukotriene B4 receptor BLT 2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes. Exp Dermatol. 2016;25(7):532–536.
  • Terrak M, Kerff F, Langsetmo K, et al. Structural basis of protein phosphatase 1 regulation. Nature. 2004;429(6993):780–784.
  • MacDonald JA, Walsh MP. Regulation of smooth muscle myosin light chain phosphatase by multi-site phosphorylation of the myosin targeting subunit, MYPT1. Cardiovascular & Haematological Disorders-Drug Targets (Formerly Current Drug Targets-Cardiovascular & Hematological Disorders). 2018;18(1):4–13.
  • Ijpma G, Matusovsky O, Lauzon A-M. Accumulating evidence for increased velocity of airway smooth muscle shortening in asthmatic airway hyperresponsiveness. J Allergy (Cairo). 2012;2012:156909.
  • Bramley A, Thomson R, Roberts C, et al. Hypothesis: excessive bronchoconstriction in asthma is due to decreased airway elastance. Eur Respir J. 1994;7(2):337–341.
  • Goldie R, Spina D, Henry P, et al. In vitro responsiveness of human asthmatic bronchus to carbachol, histamine, beta‐adrenoceptor agonists and theophylline. Br J Clin Pharmacol. 1986;22(6):669–676.
  • Björck T, Gustafsson LE, Dahlén S-E. Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine. Amer Rev Respir Dis. 1992;145(5):1087–1091.
  • Ma X, Cheng Z, Kong H, et al. Changes in biophysical and biochemical properties of single bronchial smooth muscle cells from asthmatic subjects. Am J Physiol Lung Cell Mol Physiol. 2002;283(6):L1181–L1189.
  • Sutcliffe A, Hollins F, Gomez E, et al. Increased nicotinamide adenine dinucleotide phosphate oxidase 4 expression mediates intrinsic airway smooth muscle hypercontractility in asthma. Am J Respir Crit Care Med. 2012;185(3):267–274.
  • Chapman DG, Irvin CG. Mechanisms of airway hyper‐responsiveness in asthma: the past, present and yet to come. Clin Exp Allergy. 2015;45(4):706–719.
  • Mahn K, Ojo OO, Chadwick G, et al. Ca2+ homeostasis and structural and functional remodelling of airway smooth muscle in asthma. Thorax. 2010;65(6):547–552.
  • Mahn K, Hirst SJ, Ying S, et al. Diminished sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma. Proceedings of the National Academy of Sciences. 2009;106(26):10775–10780.
  • Koopmans T, Anaparti V, Castro-Piedras I, et al. Ca2+ handling and sensitivity in airway smooth muscle: emerging concepts for mechanistic understanding and therapeutic targeting. Pulm Pharmacol Ther. 2014;29(2):108–120.
  • Sathish V, Thompson MA, Sinha S, et al. Inflammation, caveolae and CD38-mediated calcium regulation in human airway smooth muscle. Biochim Biophys Acta-Mol Cell Res. 2014;1843(2):346–351.
  • Prakash Y, Kannan MS, Sieck GC. Regulation of intracellular calcium oscillations in porcine tracheal smooth muscle cells. Am J Physiol Cell Physiol. 1997;272(3):C966–C975.
  • Prakash Y, Pabelick CM, Kannan MS, et al. Spatial and temporal aspects of ACh-induced [Ca2+]i oscillations in porcine tracheal smooth muscle. Cell calcium. 2000;27(3):153–162.
  • Deshpande DA, Dogan S, Walseth TF, et al. Modulation of calcium signaling by interleukin-13 in human airway smooth muscle: role of CD38/cyclic adenosine diphosphate ribose pathway. Am J Respir Cell Mol Biol. 2004;31(1):36–42.
  • Guedes AG, Paulin J, Rivero-Nava L, et al. CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge. Am J Physiol Lung Cell Mol Physiol. 2006;291(6):L1286–L1293.
  • Wylam ME, Sathish V, VanOosten SK, et al. Mechanisms of cigarette smoke effects on human airway smooth muscle. PloS one. 2015;10(6):e0128778.
  • Amrani Y, Krymskaya V, Maki C, et al. Mechanisms underlying TNF-α effects on agonist-mediated calcium homeostasis in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 1997;273(5):L1020–L1028.
  • Jude JA, Solway J, Panettieri JRA, et al. Differential induction of CD38 expression by TNF-α in asthmatic airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2010;299(6):L879–L890.
  • Sweeney M, McDaniel SS, Platoshyn O, et al. Role of capacitative Ca2+ entry in bronchial contraction and remodeling. J Appl Physiol. 2002;92(4):1594–1602.
  • Thakore P, Earley S. STIM1 is the key that unlocks airway smooth muscle remodeling and hyperresponsiveness during asthma. Cell Calcium. 2022;104:102589.
  • Roos J, DiGregorio PJ, Yeromin AV, et al. STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol. 2005;169(3):435–445.
  • Liou J, Kim ML, Do Heo W, et al. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol. 2005;15(13):1235–1241.
  • Spinelli AM, González-Cobos JC, Zhang X, et al. Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration. Pflügers Archiv-Euro J Physiol. 2012;464(5):481–492.
  • Johnson MT, Xin P, Benson JC, et al. STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma. Proc Natl Acad Sci U S A. 2022;119(1):e2114557118.
  • Sathish V, Abcejo AJ, Thompson MA, et al. Caveolin-1 regulation of store-operated Ca2+ influx in human airway smooth muscle. Eur Respir J. 2012;40(2):470–478.
  • Yarova PL, Stewart AL, Sathish V, et al. Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma. Sci Transl Med. 2015;7(284):284ra60–284ra60.
  • Sopi RB, Mayer CA, Martin RJ, et al. Calcium-Sensing Receptor (CaSR) Modulates Hyperoxia-Induced Airway Hyperreactivity In a Neonatal Mouse Model of Bronchopulmonary Dysplasia. FASEB J. 2020;34(S1):1–1.
  • Roesler AM, Ravix J, Bartman CM, et al. Calcium-sensing receptor contributes to hyperoxia effects on human fetal airway smooth muscle. Front Physiol. 2021;12:585895.
  • Lopez‐Fernandez I, Schepelmann M, Brennan SC, et al. The calcium‐sensing receptor: one of a kind. Exp Physiol. 2015;100(12):1392–1399.
  • T-y Z, B-h C, Zou L, et al. Expression and role of the calcium-sensing receptor in rat peripheral blood polymorphonuclear neutrophils. Oxid Med Cell Longev. 2017;2017.
  • Dershem R, Gorvin CM, Metpally RP, et al. Familial hypocalciuric hypercalcemia type 1 and autosomal-dominant hypocalcemia type 1: prevalence in a large healthcare population. Am J Hum Genet. 2020;106(6):734–747.
  • Dixon RE, Santana LF. A Ca2+-and PKC-driven regulatory network in airway smooth muscle. J General Physiol. 2013;141(2):161–164.
  • Ojiaku CA, Cao G, Zhu W, et al. TGF-β1 evokes human airway smooth muscle cell shortening and hyperresponsiveness via Smad3. Am J Respir Cell Mol Biol. 2018;58(5):575–584.
  • Chiba Y, Matsusue K, Misawa M. RhoA, a possible target for treatment of airway hyperresponsiveness in bronchial asthma. J Pharmacol Sci. 2010;114(3):239–247.
  • Chiba Y, Ueno A, Shinozaki K, et al. Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice. Respir Res. 2005;6(1):1–11.
  • Wang L, Chitano P, Paré PD, et al. Upregulation of smooth muscle Rho-kinase protein expression in human asthma. Eur Respir J. 2020;55(3).
  • Schaafsma D, Gosens R, Zaagsma J, et al. Rho kinase inhibitors: a novel therapeutical intervention in asthma? Eur J Pharmacol. 2008;585(2–3):398–406.
  • Zhang Y, Saradna A, Ratan R, et al. RhoA/Rho‐kinases in asthma: from pathogenesis to therapeutic targets. Clin Transl Immunology. 2020;9(5):e1134.
  • Sakai H, Suto W, Kai Y, et al. Mechanisms underlying the pathogenesis of hyper-contractility of bronchial smooth muscle in allergic asthma. Journal of Smooth Muscle Research. 2017;53:37–47.
  • Verhein KC, Fryer AD, Jacoby DB. Neural control of airway inflammation. Curr Allergy Asthma Rep. 2009;9(6):484–490.
  • Prakash Y, Thompson MA, Meuchel L, et al. Neurotrophins in lung health and disease. Expert Rev Respir Med. 2010;4(3):395–411.
  • Egea J, Buendia I, Parada E, et al. Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection. Biochem Pharmacol. 2015;97(4):463–472.
  • Hogg R, Raggenbass M, Bertrand D. Nicotinic acetylcholine receptors: from structure to brain function. Rev Physiol Biochem Pharmacol. 2003;1–46.
  • Hong W, Peng G, Hao B, et al. Nicotine-induced airway smooth muscle cell proliferation involves TRPC6-dependent calcium influx via α7 nAChR. Cell physiol biochem. 2017;43(3):986–1002.
  • Borkar NA, Roos B, Prakash Y, et al. Nicotinic α7 acetylcholine receptor (α7nAChR) in human airway smooth muscle. Arch Biochem Biophys. 2021;706:108897.
  • Kistemaker L, Prakash Y. Airway innervation and plasticity in asthma. Physiology. 2019;34(4):283–298.
  • Renz H. Neurotrophins in bronchial asthma. Respir Res. 2001;2(5):1–4.
  • Papi A, Blasi F, Canonica GW, et al. Treatment strategies for asthma: reshaping the concept of asthma management. Allergy Asthma Clin Immunol. 2020;16(1):1–11.
  • Henderson I, Caiazzo E, McSharry C, et al. Why do some asthma patients respond poorly to glucocorticoid therapy? Pharmacol Res. 2020;160:105189.
  • Lang DM, editor Severe asthma: epidemiology, burden of illness, and heterogeneity. Allergy & Asthma Proceedings; 2015.
  • Durrani SR, Viswanathan RK, Busse WW. What effect does asthma treatment have on airway remodeling? Current perspectives. Journal of Allergy and Clinical Immunology. 2011;128(3):439–448.
  • Salem IH, Boulet L-P, Biardel S, et al. Long-term effects of bronchial thermoplasty on airway smooth muscle and reticular basement membrane thickness in severe asthma. Ann Am Thorac Soc. 2016;13(8):1426–1428.
  • Calzetta L, Aiello M, Frizzelli A, et al. The impact of monoclonal antibodies on airway smooth muscle contractility in asthma: a systematic review. Biomedicines. 2021;9(9):1281.
  • Lukovic E, Emala C. Diacylglycerol Kinase Puts the Brakes on Airway Smooth Muscle Contraction. American Thoracic Society; 2021. p. 578–580.
  • Sharma P, Yadav SK, Shah SD, et al. Diacylglycerol kinase inhibition reduces airway contraction by negative feedback regulation of Gq-signaling. Am J Respir Cell Mol Biol. 2021;65(6):658–671.
  • Singh BK, Lu W, Schmidt Paustian AM, et al. Diacylglycerol kinase ζ promotes allergic airway inflammation and airway hyperresponsiveness through distinct mechanisms. Sci Signal. 2019;12(597):eaax3332.
  • KleinJan A. Airway inflammation in asthma: key players beyond the Th2 pathway. Curr Opin Pulm Med. 2016;22(1):46–52.
  • Penn RB. Calcilytics for asthma relief. Science. 2015;348(6233):398–399.
  • Deshpande DA, Guedes AG, Lund FE, et al. CD38 in the pathogenesis of allergic airway disease: potential therapeutic targets. Pharmacol Ther. 2017;172:116–126.
  • Liu P, Li S, Tang L. Nerve growth factor: a potential therapeutic target for lung diseases. Int J Mol Sci. 2021;22(17):9112.
  • Britt JRD, Thompson MA, Wicher SA, et al. Smooth muscle brain‐derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma. FASEB J. 2019;33(2):3024–3034.
  • Hernandez-Lara MA, Yadav SK, Shah SD, et al. Regulation of Airway Smooth Muscle Cell Proliferation by Diacylglycerol Kinase: relevance to Airway Remodeling in Asthma. Int J Mol Sci. 2022;23(19):11868.
  • Camoretti-Mercado B, Lockey RF. Bitter taste receptors in the treatment of asthma: opportunities and challenges. J Allergy Clin Immunol. 2020;146(4):776–779.
  • Nayak AP, Shah SD, Michael JV, et al. Bitter taste receptors for asthma therapeutics. Front Physiol. 2019;10:884.
  • Gerthoffer WT, Solway J, Camoretti-Mercado B. Emerging targets for novel therapy of asthma. Curr Opin Pharmacol. 2013;13(3):324–330.
  • Nayak AP, An SS. Anxiolytics for Bronchodilation: refinements to GABAA Agonists for Asthma Relief. 2022 ;64(4):419–420.
  • Forkuo GS, Nieman AN, Kodali R, et al. A novel orally available asthma drug candidate that reduces smooth muscle constriction and inflammation by targeting GABAA receptors in the lung. Mol Pharm. 2018;15(5):1766–1777.
  • Gallos G, Yocum GT, Siviski ME, et al. Selective targeting of the α5-subunit of GABAA receptors relaxes airway smooth muscle and inhibits cellular calcium handling. Am J Physiol Lung Cell Mol Physiol. 2015;308(9):L931–L942.
  • Duan W, Wong WF. Targeting mitogen-activated protein kinases for asthma. Curr Drug Targets. 2006;7(6):691–698.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.