Bartis, Domokos

Mahida, Rahul

Thickett, David

English

University of Birmingham Research Portal

  University of BirminghamWnt 11 inhibits the effects of transforming growthfactor-1 (TGF-1) on lung epithelial phenotypeMahida, Rahul; Bartis, Domokos; Thickett, DavidDocument VersionPublisher's PDF, also known as Version of recordCitation for published version (Harvard):Mahida, R, Bartis, D & Thickett, D 2013, 'Wnt 11 inhibits the effects of transforming growth factor-1 (TGF-1) onlung epithelial phenotype'.Link to publication on Research at Birmingham portalGeneral rightsUnless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or thecopyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposespermitted by law.•	Users may freely distribute the URL that is used to identify this publication.•	Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of privatestudy or non-commercial research.•	User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?)•	Users may not further distribute the material nor use it for the purposes of commercial gain.Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.When citing, please reference the published version.Take down policyWhile the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has beenuploaded in error or has been deemed to be commercially or otherwise sensitive.If you believe that this is the case for this document, please contact UBIRA@lists.bham.ac.uk providing details and we will remove access tothe work immediately and investigate.Download date: 01. Mar. 2020Background Transforming Growth Factor-β1 (TGFβ1) induces epithelial-to-mesenchymal transition (EMT) in alveolar type 2 (ATII) cells in vitro. This process is implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). SMADs are transcription factors activated by TGFβ1 signalling. When the TGFβ1 signalling pathway is activated, SMAD translocates from the cytoplasm to the nucleus. Wnt11 is a conserved glycoprotein secreted by macrophages and some ATII cells in the adult lung. Wnts bind to Frizzled (Fz) receptors. Previous work has shown that Wnt11 appears to inhibit both spontaneous and TGFβ1-driven EMT in ATII cell cultures. Aims: To investigate the role of Wnt11 – Frizzled receptor signalling on EMT in human ATII cells Results Wnt11 inhibits expression of mesenchymal markers & promotes expression of epithelial markers in cells treated with TGFβ1 (data not shown). Wnt11 inhibits TGFβ1-mediated migration of A549s and promotes A549 proliferation. Silencing Fz2 leads to increased expression of SMAD. Wnt11 inhibits SMAD nuclear translocation.  Methods A549 cancer cell lines were used as a model for type II alveolar cells. We used 2 types of transgenic A549 cells, created by infecting cells with lentivirus vectors A549 cells which stably express Wnt11 and GFP A549 cells which stable express GFP alone (used as control). A549s were treated with 10ng/ml TGFβ1 for 24 hours. SiRNAs targeted against mRNA coding for frizzled receptors were used to create a temporary “knockdown” effect. Epithelial and mesenchymal marker expression was assessed using RT-qPCR and FACS. BrdU proliferation assays & wound healing assays. Confocal microscopy was used to observe intracellular SMAD distribution.           Conclusions The Wnt11-Fz2 and TGFβ-SMAD signalling pathways appear to be antagonistic, with the Wnt11 pathway opposing TGFβ-mediated EMT. Future therapies directed at promoting the Wnt11 may potentially be used in IPF.       Wnt 11 inhibits the effects of transforming growth factor-β1 (TGF-β1) on lung epithelial phenotype Dr R. Mahida, Dr D. Bartis, Dr D. Thickett Respiratory Research Group, University of Birmingham, UK.  

Wnt 11 inhibits the effects of transforming growth factor-β1 (TGF-β1) on lung epithelial phenotype

http://pure-oai.bham.ac.uk/ws/files/28281474/ERS_Poster_RAHUL_MAHIDA.pdf

Wnt 11 inhibits the effects of transforming growth factor-β1 (TGF-β1) on lung epithelial phenotype

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