Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/155003
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dc.titleCD151, a laminin receptor showing increased expression in asthmatic patients, contributes to airway hyperresponsiveness through calcium signaling
dc.contributor.authorQiao, Yongkang
dc.contributor.authorTam, John Kit Chung
dc.contributor.authorTan, Sheryl SL
dc.contributor.authorTai, Yee Kit
dc.contributor.authorChin, Chin Yein
dc.contributor.authorStewart, Alastair G
dc.contributor.authorAshman, Leonie
dc.contributor.authorSekiguchi, Kiyotoshi
dc.contributor.authorLangenbach, Shenna Y
dc.contributor.authorStelmack, Gerald
dc.contributor.authorHalayko, Andrew J
dc.contributor.authorTran, Thai
dc.date.accessioned2019-06-03T04:06:27Z
dc.date.available2019-06-03T04:06:27Z
dc.date.issued2017-01-01
dc.identifier.citationQiao, Yongkang, Tam, John Kit Chung, Tan, Sheryl SL, Tai, Yee Kit, Chin, Chin Yein, Stewart, Alastair G, Ashman, Leonie, Sekiguchi, Kiyotoshi, Langenbach, Shenna Y, Stelmack, Gerald, Halayko, Andrew J, Tran, Thai (2017-01-01). CD151, a laminin receptor showing increased expression in asthmatic patients, contributes to airway hyperresponsiveness through calcium signaling. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 139 (1) : 82-+. ScholarBank@NUS Repository.
dc.identifier.issn0091-6749
dc.identifier.issn1097-6825
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/155003
dc.description.abstract© 2016 American Academy of Allergy, Asthma & Immunology Background Airway smooth muscle (ASM) contraction underpins airway constriction; however, underlying mechanisms for airway hyperresponsiveness (AHR) remain incompletely defined. CD151, a 4-transmembrane glycoprotein that associates with laminin-binding integrins, is highly expressed in the human lung. The role of CD151 in ASM function and its relationship to asthma have yet to be elucidated. Objective We sought to ascertain whether CD151 expression is clinically relevant to asthma and whether CD151 expression affects AHR. Methods Using immunohistochemical analysis, we determined the expression of CD151 in human bronchial biopsy specimens from patients with varying asthma severities and studied the mechanism of action of CD151 in the regulation of ASM contraction and bronchial caliber in vitro, ex vivo, and in vivo. Results The number of CD151+ ASM cells is significantly greater in patients with moderate asthma compared with those in healthy nonasthmatic subjects. From loss- and gain-of-function studies, we reveal that CD151 is required for and enhances G protein–coupled receptor (GPCR)–induced peak intracellular calcium release, the primary determinant of excitation-contraction coupling. We show that the localization of CD151 can also be perinuclear/cytoplasmic and offer an explanation for a novel functional role for CD151 in supporting protein kinase C (PKC) translocation to the cell membrane in GPCR-mediated ASM contraction at this site. Importantly, CD151−/− mice are refractory to airway hyperreactivity in response to allergen challenge. Conclusions We identify a role for CD151 in human ASM contraction. We implicate CD151 as a determinant of AHR in vivo, likely through regulation of GPCR-induced calcium and PKC signaling. These observations have significant implications in understanding the mechanism for AHR and the efficacy of new and emerging therapeutics.
dc.language.isoen
dc.publisherMOSBY-ELSEVIER
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectAllergy
dc.subjectImmunology
dc.subjectAirway hyperresponsiveness
dc.subjectairway smooth muscle
dc.subjectasthma
dc.subjectcontraction
dc.subjectcalcium
dc.subjectCD151
dc.subjectG protein-coupled receptor
dc.subjectintegrins
dc.subjectlaminin
dc.subjectPKC
dc.subjecttetraspanin
dc.subjectSMOOTH-MUSCLE-CELLS
dc.subjectTETRASPANIN CD151
dc.subjectTH2 LYMPHOCYTES
dc.subjectRENAL-DISEASE
dc.subjectPHENOTYPE
dc.subjectMICE
dc.subjectCA2+
dc.subjectHYPERCONTRACTILE
dc.subjectCARCINOGENESIS
dc.typeArticle
dc.date.updated2019-06-03T02:30:52Z
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.contributor.departmentDEPT OF SURGERY
dc.contributor.departmentDEAN'S OFFICE (MEDICINE)
dc.description.sourcetitleJOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
dc.description.volume139
dc.description.issue1
dc.description.page82-+
dc.description.codenJACIB
dc.published.statePublished
dc.grant.idNMRC/1215/2009
dc.grant.id1045372
dc.grant.id1059665
dc.grant.fundingagencyCIHR, Canadian Institutes of Health Research
dc.grant.fundingagencyNHMRC, National Health and Medical Research Council
dc.grant.fundingagencyCanada Research Chairs
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