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. 2022 Feb;113(1):4-16.
doi: 10.23736/S0026-4806.21.07283-9. Epub 2021 Jan 26.

Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction

Eric B Gebski  1 , Omkar Anaspure  1 , Reynold A Panettieri  1 , Cynthia J Koziol-White  2
Affiliations

Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction

Eric B Gebski et al. Minerva Med. 2022 Feb.

Abstract

Airway smooth muscle plays a pivotal role in modulating bronchomotor tone. Modulation of contractile and relaxation signaling is critical to alleviate the airway hyperresponsiveness (AHR) associated with asthma. Emerging studies examining the phenotype of ASM in the context of asthma provide rich avenues to develop more effective therapeutics to attenuate the AHR associated with the disease.

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Figures

Figure 1.—
Figure 1.—
Calcium-dependent and –independent, and nerve-mediated, pathways which modulate ASM contraction and AHR. cADPR, cyclic-ADP-ribose; CaM, calmodulin; CD38, cluster of differentiation 38; CICR, Ca2+-induced Ca2+ release; DAG, sn-1,2-diacylglycerol; GEF, guanidine nucleotide exchange factors; IP3, inositol-1,4,5-trisphosphate; IP3R, inositol-1,4,5-trisphosphate receptor; MLC, myosin light chain; MLCK, myosin light-chain kinase; MYPT1, myosin phosphatase target subunit-1 of myosin light-chain phosphatase (MLCP); Orai1, store operated channel proteins; PIP2, phosphatidylinositol (4,5 )-bis phosphate; RhoA-GDP, inactive form of RhoA; RhoA-GTP, active form of RhoA; ROCK, Rho-associated kinase; RyR, ryanodine receptor; SERCA, sarcoendoplasmic reticulum calcium ATPase; STIM1, stromal interaction molecule 1; BDNF, brain-derived neurotrophic factor; NT4, neurotrophin 4 receptor; TrkB, tropomyosin receptor kinase B/p75 neurotrophin receptor; TRPC, transient receptor potential cation channel 3/6; PLC beta, phospholipase C.
Figure 2.—
Figure 2.—
Actin remodeling pathways which modulate ASM contraction and AHR. C-Abl, c-abl tyrosine kinase; Abi1, c-Abl adaptor 1; N-WASP, neural wiskott-aldrich protein; Arp2/3, actin-related protein 2/3; GMFγ, glia maturation factor γ; Pfn-1, profilin-1; CAS/CrkII, Crk-associated substrate.
Figure 3.—
Figure 3.—
β2 adrenergic receptor (β2AR)-mediated inhibition of contractile signaling, signaling pathways modulating relaxation, and mechanisms of β2AR downregulation. RGS2/4/5, regulator of g protein signaling 2/4/5; βarr, β arrestin 1/2; PDE3/4, phosphodiesterase 3/4; GRK2/3, G protein receptor kinase 2/3; Epac, exchange factor directly activated by cAMP; PKA, protein kinase A; ADP, adenosine diphosphate; cAMP, cyclic adenosine monophosphate; AC, adenylyl cyclase.
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References

    1. An SS, Bai TR, Bates JH, Black JL, Brown RH, Brusasco V, et al. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma. Eur Respir J 2007:29:834–60. - PMC - PubMed
    1. An SS, Kim J, Ahn K, Trepat X, Drake KJ, Kumar S, et al. Cell stiffness, contractile stress and the role of extracellular matrix. Biochem Biophys Res Commun 2009;382:697–703. - PMC - PubMed
    1. An SS, Mitzner W, Tang WY, Ahn K, Yoon AR, Huang J, et al. An inflammation-independent contraction mechanophenotype of airway smooth muscle in asthma. J Allergy Clin Immunol 2016;138:294–297.e4. - PMC - PubMed
    1. Amrani Y, Krymskaya V, Maki C, Panettieri RA Jr. Mechanisms underlying TNF-alpha effects on agonist-mediated calcium homeostasis in human airway smooth muscle cells. Am J Physiol 1997;273:L1020–8. - PubMed
    1. Croisier H, Tan X, Chen J, Sneyd J, Sanderson MJ, Brook BS. Ryanodine receptor sensitization results in abnormal calcium signaling in airway smooth muscle cells. Am J Respir Cell Mol Biol 2015;53:703–11. - PMC - PubMed