The hippo pathway effector Yes‐associated protein promotes epithelial proliferation and remodeling in chronic rhinosinusitis with nasal polyps

AllergyVolume 74, Issue 4 p. 731-742 ORIGINAL ARTICLE The hippo pathway effector Yes-associated protein promotes epithelial proliferation and remodeling in chronic rhinosinusitis with nasal polyps Huiyi Deng, Huiyi Deng Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorYueqi Sun, Yueqi Sun orcid.org/0000-0002-2382-0429 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorWeihao Wang, Weihao Wang Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorMeijiao Li, Meijiao Li Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorTian Yuan, Tian Yuan Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorWeifeng Kong, Weifeng Kong Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorXuekun Huang, Xuekun Huang Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorZijie Long, Zijie Long Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorZhuanggui Chen, Zhuanggui Chen Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorDeyun Wang, Corresponding Author Deyun Wang entwdy@nus.edu.sg orcid.org/0000-0002-0909-2963 Department of Otolaryngology, National University Health System, National University of Singapore, Singapore, Singapore Correspondence Deyun Wang, Department of Otolaryngology-Head and Neck Surgery, National University Health System, National University of Singapore, Singapore, Singapore. Email: entwdy@nus.edu.sg and Qintai Yang, Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Email: yang.qt@163.comSearch for more papers by this authorQintai Yang, Corresponding Author Qintai Yang yang.qt@163.com orcid.org/0000-0003-3377-737X Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Correspondence Deyun Wang, Department of Otolaryngology-Head and Neck Surgery, National University Health System, National University of Singapore, Singapore, Singapore. Email: entwdy@nus.edu.sg and Qintai Yang, Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Email: yang.qt@163.comSearch for more papers by this author Huiyi Deng, Huiyi Deng Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorYueqi Sun, Yueqi Sun orcid.org/0000-0002-2382-0429 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorWeihao Wang, Weihao Wang Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorMeijiao Li, Meijiao Li Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorTian Yuan, Tian Yuan Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorWeifeng Kong, Weifeng Kong Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorXuekun Huang, Xuekun Huang Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorZijie Long, Zijie Long Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorZhuanggui Chen, Zhuanggui Chen Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorDeyun Wang, Corresponding Author Deyun Wang entwdy@nus.edu.sg orcid.org/0000-0002-0909-2963 Department of Otolaryngology, National University Health System, National University of Singapore, Singapore, Singapore Correspondence Deyun Wang, Department of Otolaryngology-Head and Neck Surgery, National University Health System, National University of Singapore, Singapore, Singapore. Email: entwdy@nus.edu.sg and Qintai Yang, Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Email: yang.qt@163.comSearch for more papers by this authorQintai Yang, Corresponding Author Qintai Yang yang.qt@163.com orcid.org/0000-0003-3377-737X Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Correspondence Deyun Wang, Department of Otolaryngology-Head and Neck Surgery, National University Health System, National University of Singapore, Singapore, Singapore. Email: entwdy@nus.edu.sg and Qintai Yang, Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Email: yang.qt@163.comSearch for more papers by this author First published: 26 October 2018 https://doi.org/10.1111/all.13647Citations: 18 Deng, Sun and Wang equally contributed to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Background Hippo-Yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and development. However, its possible role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. We aim to investigate it on nasal epithelial proliferation and remodeling in CRSwNP. Methods The expressions of hippo pathway components as well as Ki-67 and E-cadherin in the sinonasal mucosa and nasal epithelial cells were analyzed in 14 controls, 14 eosinophilic CRSwNP, and 14 noneosinophilic CRSwNP. Nasal epithelial cells from 6 controls, 6 eosinophilic CRSwNP, and 6 noneosinophilic CRSwNP were cultured and treated with lipopolysaccharide (LPS), Poly(I:C), or a selective YAP inhibitor verteporfin (VP). Results The hippo pathway components MST1, LATS1/2, YAP, and TEAD1 were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells, along with upregulation of Ki-67 and downregulation of E-cadherin. The mRNA levels of YAP positively correlated with the Ki-67 mRNA levels, and negatively associated with the E-cadherin mRNA levels in polyp tissues and epithelial cells from nasal polyps (NPECs). LPS and Poly(I:C) upregulated the YAP expression in nasal epithelial cells accompanied by increased TEAD1 and Ki-67 expression. Conversely, YAP inhibition by VP decreased TEAD1 and Ki-67 expression in NPECs. Conclusions Hippo pathway components are abnormally upregulated in NPECs, and its effector YAP promotes nasal epithelial cells proliferation and remodeling in CRSwNP. It provides a rationale to explore inhibition of YAP as a novel therapeutic strategy for reducing the epithelial proliferation and remodeling in CRSwNP. CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest. Citing Literature Supporting Information Filename Description all13647-sup-0001-FigS1-S7.pdfPDF document, 2.5 MB all13647-sup-0002-Supinfo.docxWord document, 26.9 KB Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume74, Issue4April 2019Pages 731-742 RelatedInformation