scholarly journals Network and co-expression analysis of airway smooth muscle cell transcriptome delineates potential gene signatures in asthma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Priyanka Banerjee ◽  
Premanand Balraj ◽  
Nilesh Sudhakar Ambhore ◽  
Sarah A. Wicher ◽  
Rodney D. Britt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Molecular Mechanisms ◽  
Airway Smooth Muscle Cell ◽  
Gene Interactions ◽  
Regulatory Relationship ◽  
Multiple Gene ◽  
Asthma Exacerbations ◽  
Asthmatic Group

AbstractAirway smooth muscle (ASM) is known for its role in asthma exacerbations characterized by acute bronchoconstriction and remodeling. The molecular mechanisms underlying multiple gene interactions regulating gene expression in asthma remain elusive. Herein, we explored the regulatory relationship between ASM genes to uncover the putative mechanism underlying asthma in humans. To this end, the gene expression from human ASM was measured with RNA-Seq in non-asthmatic and asthmatic groups. The gene network for the asthmatic and non-asthmatic group was constructed by prioritizing differentially expressed genes (DEGs) (121) and transcription factors (TFs) (116). Furthermore, we identified differentially connected or co-expressed genes in each group. The asthmatic group showed a loss of gene connectivity due to the rewiring of major regulators. Notably, TFs such as ZNF792, SMAD1, and SMAD7 were differentially correlated in the asthmatic ASM. Additionally, the DEGs, TFs, and differentially connected genes over-represented in the pathways involved with herpes simplex virus infection, Hippo and TGF-β signaling, adherens junctions, gap junctions, and ferroptosis. The rewiring of major regulators unveiled in this study likely modulates the expression of gene-targets as an adaptive response to asthma. These multiple gene interactions pointed out novel targets and pathways for asthma exacerbations.

scholarly journals Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating Hippo signaling effector YAP

2018 ◽  
Vol 315 (4) ◽  
pp. L609-L621 ◽  
Author(s):  
Lu Liu ◽  
Cui Zhai ◽  
Yilin Pan ◽  
Yanting Zhu ◽  
Wenhua Shi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Cyclin D1 ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Molecular Mechanisms ◽  
Airway Smooth Muscle Cell ◽  
Hippo Signaling ◽  
Rock Inhibitor ◽  
Sphingosine 1 Phosphate

Sphingosine-1-phosphate (S1P), a bioactive lipid, has been shown to be elevated in the airways of individuals with asthma and modulates the airway smooth muscle cell (ASMC) functions, yet its underlying molecular mechanisms are not completely understood. The aim of the present study is to address this issue. S1P induced yes-associated protein (YAP) dephosphorylation and nuclear localization via the S1PR2/3/Rho-associated protein kinase (ROCK) pathway, and this in turn increased forkhead box M1 (FOXM1) and cyclin D1 expression leading to ASMC proliferation, migration, and contraction. Pretreatment of cells with S1PR2 antagonist JTE013, S1PR3 antagonist CAY10444, or ROCK inhibitor Y27632 blocked S1P-induced alterations of YAP, FOXM1, cyclin D1, and ASMC proliferation, migration, and contraction. In addition, prior silencing of YAP or FOXM1 with siRNA reversed the effect of S1P on ASMC functions. Taken together, our study indicates that S1P stimulates ASMC proliferation, migration, and contraction by binding to S1PR2/3 and modulating ROCK/YAP/FOXM1 axis and suggests that targeting this pathway might have potential value in the management of asthma.

A human airway smooth muscle cell line that retains physiological responsiveness

1989 ◽  
Vol 256 (2) ◽  
pp. C329-C335 ◽  
Author(s):  
R. A. Panettieri ◽  
R. K. Murray ◽  
L. R. DePalo ◽  
P. A. Yadvish ◽  
M. I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Cell Line ◽  
Airway Smooth Muscle ◽  
Cytosolic Calcium ◽  
Airway Smooth Muscle Cell ◽  
Airway Smooth Muscle Cells ◽  
Functional Coupling ◽  
Functional Responses ◽  
Human Airway Smooth Muscle ◽  
Human Airway

We report the development of a nontransformed line of human airway smooth muscle cells retaining smooth muscle-specific contractile protein expression and physiological responsiveness to agonists implicated in inflammatory airway diseases. Specific responses to histamine, leukotrienes, bradykinin, platelet-activating factor, substance P, and thromboxane analogues are demonstrated as well as functional coupling to beta-adrenergic receptors. The cell line was characterized using indirect immunofluorescence, as well as electrophoretic separation and immunoblot analysis of smooth muscle-specific actin. Functional responses were assessed by measurements of cytosolic calcium and stimulation of adenosine 3',5'-cyclic monophosphate production. The cells retain their responsiveness over many population doublings and should be a useful model to examine specific receptor-effector mechanisms, as well as the effects of neurohumoral agents on the regulation of airway smooth muscle growth and differentiation.

scholarly journals Novel phosphodiesterases inhibitors from the group of purine-2,6-dione derivatives as potent modulators of airway smooth muscle cell remodelling

2019 ◽  
Vol 865 ◽  
pp. 172779 ◽  
Author(s):  
Katarzyna Wójcik-Pszczoła ◽  
Grażyna Chłoń-Rzepa ◽  
Agnieszka Jankowska ◽  
Eugenie Ellen ◽  
Artur Świerczek ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Airway Smooth Muscle Cell

Cytoskeletal mechanics in adherent human airway smooth muscle cells: probe specificity and scaling of protein-protein dynamics

2004 ◽  
Vol 287 (3) ◽  
pp. C643-C654 ◽  
Author(s):  
Marina Puig-de-Morales ◽  
Emil Millet ◽  
Ben Fabry ◽  
Daniel Navajas ◽  
Ning Wang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Dynamics ◽  
Airway Smooth Muscle ◽  
Power Law ◽  
Density Lipoprotein ◽  
Airway Smooth Muscle Cell ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Lateral Displacements

We probed elastic and loss moduli in the adherent human airway smooth muscle cell through a variety of receptor systems, each serving as a different molecular window on cytoskeletal dynamics. Coated magnetic microbeads were attached to the cell surface via coating-receptor binding. A panel of bead coatings was investigated: a peptide containing the sequence RGD, vitronectin, urokinase, activating antibody against β1-integrin, nonactivating antibody against β1-integrin, blocking antibody against β1-integrin, antibody against β1-integrin, and acetylated low-density lipoprotein. An oscillatory mechanical torque was applied to the bead, and resulting lateral displacements were measured at baseline, after actin disruption by cytochalasin D, or after contractile activation by histamine. As expected, mechanical moduli depended strongly on bead type and bead coating, differing at the extremes by as much as two orders of magnitude. In every case, however, elastic and loss moduli increased with frequency f as a weak power law, f  x−1. Moreover, with few exceptions, data could be scaled such that elastic and frictional responses depended solely on the power law exponent x. Taken together, these data suggest that power law behavior represents a generic feature of underlying protein-protein dynamics.

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