Inhibition of glycogen synthase kinase 3-b is sufficient but not required for airway smooth muscle hypertrophy.
dc.contributor.author | Deng, H | |
dc.contributor.author | Hershenson, MB | |
dc.contributor.author | Bentley, JK | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-10-25T12:32:36Z | |
dc.date.available | 2023-10-25T12:32:36Z | |
dc.date.issued | 2008-04-11 | |
dc.identifier.issn | 0021-9258 | |
dc.identifier.issn | 1083-351X | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/18252708 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/191157 | en |
dc.description.abstract | We examined the role of glycogen synthase kinase-3β (GSK-3β) inhibition in airway smooth muscle hypertrophy, a structural change found in patients with severe asthma. LiCl, SB216763, and specific small interfering RNA (siRNA) against GSK-3β, each of which inhibit GSK-3β activity or expression, increased human bronchial smooth muscle cell size, protein synthesis, and expression of the contractile proteins α-smooth muscle actin, myosin light chain kinase, smooth muscle myosin heavy chain, and SM22. Similar results were obtained following treatment of cells with cardiotrophin (CT)-1, a member of the interleukin-6 superfamily, and transforming growth factor (TGF)-β, a proasthmatic cytokine. GSK-3β inhibition increased mRNA expression of α-actin and transactivation of nuclear factors of activated T cells and serum response factor. siRNA against eukaryotic translation initiation factor 2Bε (eIF2Bε) attenuated LiCl- and SB216763-induced protein synthesis and expression of α-actin and SM22, indicating that eIF2B is required for GSK-3β-mediated airway smooth muscle hypertrophy. eIF2Bε siRNA also blocked CT-1- but not TGF-β-induced protein synthesis. Infection of human bronchial smooth muscle cells with pMSCV GSK-3β-A9, a retroviral vector encoding a constitutively active, nonphosphorylatable GSK-3β, blocked protein synthesis and α-actin expression induced by LiCl, SB216763, and CT-1 but not TGF-β. Finally, lungs from ovalbumin-sensitized and -challenged mice demonstrated increased α-actin and CT-1 mRNA expression, and airway myocytes isolated from ovalbumin-treated mice showed increased cell size and GSK-3β phosphorylation. These data suggest that inhibition of the GSK-3β/ eIF2Bε translational control pathway contributes to airway smooth muscle hypertrophy in vitro and in vivo. On the other hand, TGF-β-induced hypertrophy does not depend on GSK-3β/eIF2B signaling. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc. | |
dc.format.medium | Print-Electronic | |
dc.publisher | Elsevier | |
dc.rights | Licence for published version: Creative Commons Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Animals | |
dc.subject | Asthma | |
dc.subject | Bronchi | |
dc.subject | Cytokines | |
dc.subject | Enzyme Inhibitors | |
dc.subject | Eukaryotic Initiation Factor-2B | |
dc.subject | Glycogen Synthase Kinase 3 | |
dc.subject | Glycogen Synthase Kinase 3 beta | |
dc.subject | Humans | |
dc.subject | Hypertrophy | |
dc.subject | Indoles | |
dc.subject | Lithium Chloride | |
dc.subject | Maleimides | |
dc.subject | Mice | |
dc.subject | Muscle Proteins | |
dc.subject | Muscle, Smooth | |
dc.subject | Protein Biosynthesis | |
dc.subject | RNA, Small Interfering | |
dc.subject | Signal Transduction | |
dc.title | Inhibition of glycogen synthase kinase 3-b is sufficient but not required for airway smooth muscle hypertrophy. | |
dc.type | Conference Paper | |
dc.identifier.pmid | 18252708 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/191157/2/10198.pdf | |
dc.identifier.doi | 10.1074/jbc.M800624200 | |
dc.identifier.doi | https://dx.doi.org/10.7302/21546 | |
dc.identifier.source | Proc Am Thorac Soc | |
dc.description.version | Published version | |
dc.date.updated | 2023-10-25T12:32:32Z | |
dc.identifier.orcid | 0000-0001-9436-5593 | |
dc.identifier.orcid | 0000-0001-8865-7979 | |
dc.description.filedescription | Description of 10198.pdf : Published version | |
dc.identifier.volume | 4 | |
dc.identifier.issue | 15 | |
dc.identifier.startpage | 10198 | |
dc.identifier.endpage | 10207 | |
dc.identifier.name-orcid | Deng, H | |
dc.identifier.name-orcid | Hershenson, MB; 0000-0001-9436-5593 | |
dc.identifier.name-orcid | Bentley, JK; 0000-0001-8865-7979 | |
dc.working.doi | 10.7302/21546 | en |
dc.owningcollname | Pediatrics and Communicable Diseases, Department of |
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