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dc.contributor.authorMoheimani, F.
dc.contributor.authorRoth, H.M.
dc.contributor.authorCross, J.
dc.contributor.authorReid, A.T.
dc.contributor.authorShaheen, F.
dc.contributor.authorWarner, S.M.
dc.contributor.authorHirota, J.A.
dc.contributor.authorKicic, Anthony
dc.contributor.authorHallstrand, T.S.
dc.contributor.authorKahn, M.
dc.contributor.authorStick, S.M.
dc.contributor.authorHansbro, P.M.
dc.contributor.authorHackett, T.L.
dc.contributor.authorKnight, D.A.
dc.date.accessioned2019-11-10T02:16:27Z
dc.date.available2019-11-10T02:16:27Z
dc.date.issued2015
dc.identifier.citationMoheimani, F. and Roth, H.M. and Cross, J. and Reid, A.T. and Shaheen, F. and Warner, S.M. and Hirota, J.A. et al. 2015. Disruption of β-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair. International Journal of Biochemistry and Cell Biology. 68: pp. 59-69.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/76815
dc.identifier.doi10.1016/j.biocel.2015.08.014
dc.description.abstract

© 2015 Elsevier Ltd. The epithelium of asthmatics is characterized by reduced expression of E-cadherin and increased expression of the basal cell markers ck-5 and p63 that is indicative of a relatively undifferentiated repairing epithelium. This phenotype correlates with increased proliferation, compromised wound healing and an enhanced capacity to undergo epithelial-mesenchymal transition (EMT). The transcription factor β-catenin plays a vital role in epithelial cell differentiation and regeneration, depending on the co-factor recruited. Transcriptional programs driven by the β-catenin/CBP axis are critical for maintaining an undifferentiated and proliferative state, whereas the β-catenin/p300 axis is associated with cell differentiation. We hypothesized that disrupting the β-catenin/CBP signaling axis would promote epithelial differentiation and inhibit EMT. We treated monolayer cultures of human airway epithelial cells with TGFβ1 in the presence or absence of the selective small molecule ICG-001 to inhibit β-catenin/CBP signaling. We used western blots to assess expression of an EMT signature, CBP, p300, β-catenin, fibronectin and ITGβ1 and scratch wound assays to assess epithelial cell migration. Snai-1 and -2 expressions were determined using q-PCR. Exposure to TGFβ1 induced EMT, characterized by reduced E-cadherin expression with increased expression of α-smooth muscle actin and EDA-fibronectin. Either co-treatment or therapeutic administration of ICG-001 completely inhibited TGFβ1-induced EMT. ICG-001 also reduced the expression of ck-5 and -19 independent of TGFβ1. Exposure to ICG-001 significantly inhibited epithelial cell proliferation and migration, coincident with a down regulation of ITGβ1 and fibronectin expression. These data support our hypothesis that modulating the β-catenin/CBP signaling axis plays a key role in epithelial plasticity and function.

dc.languageEnglish
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiochemistry & Molecular Biology
dc.subjectCell Biology
dc.subjectAirway epithelium
dc.subjectbeta-Catenin/CBP
dc.subjectICG-001
dc.subjectEpithelial-mesenchymal transition
dc.subjectWound repair
dc.subjectSUBMUCOSAL GLAND MORPHOGENESIS
dc.subjectASTHMATIC EPITHELIUM
dc.subjectDYSREGULATED REPAIR
dc.subjectTUMOR-SUPPRESSOR
dc.subjectPROTEIN CBP
dc.subjectCELLS
dc.subjectEXPRESSION
dc.subjectFIBROSIS
dc.subjectPATHWAY
dc.subjectLUNG
dc.titleDisruption of β-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair
dc.typeJournal Article
dcterms.source.volume68
dcterms.source.startPage59
dcterms.source.endPage69
dcterms.source.issn1357-2725
dcterms.source.titleInternational Journal of Biochemistry and Cell Biology
dc.date.updated2019-11-10T02:16:23Z
curtin.departmentSchool of Public Health
curtin.accessStatusFulltext not available
curtin.facultyFaculty of Health Sciences
curtin.contributor.orcidKicic, Anthony [0000-0002-0008-9733]
dcterms.source.eissn1878-5875
curtin.contributor.scopusauthoridKicic, Anthony [6507472922]


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