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http://dx.doi.org/10.14348/molcells.2019.2418

Upregulation of FZD5 in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Epigenetic Modification  

Kim, Jong-Yeup (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University)
Cha, Min-Ji (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University)
Park, Young-Seon (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University)
Kang, Jaeku (Myunggok Medical Research Institute, College of Medicine, Konyang University)
Choi, Jong-Joong (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University)
In, Seung Min (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University)
Kim, Dong-Kyu (Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital)
Publication Information
Molecules and Cells / v.42, no.4, 2019 , pp. 345-355 More about this Journal
Abstract
Eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most challenging problems in clinical rhinology. FZD5 is a receptor for Wnt5A, and its complex with Wnt5A contributes to activating inflammation and tissue modification. Nasal polyps and eosinophil/non-eosinophil counts are reported to be directly correlated. This study investigated the expression and distribution of FZD5, and the role of eosinophil infiltration and FZD5 in eosinophilic CRSwNP pathogenesis. The prognostic role of eosinophil levels was evaluated in seven patients with CRSwNP. Fifteen patients with CRS were classified based on the percentage of eosinophils in nasal polyp tissue. Methylated genes were detected using methylCpG-binding domain sequencing, and qRT-PCR and immunohistochemistry were used to detect FZD5 expression in nasal polyp tissue samples. The results showed that mRNA expression of FZD5 was upregulated in nasal polyps. FZD5 expression was significantly higher in nasal polyp samples from patients with eosinophilic CRSwNP than in those from patients with non-eosinophilic CRSwNP, as indicated by immunohistochemistry. Furthermore, inflammatory cytokine levels were higher in eosinophilic CRSwNP-derived epithelial cells than in normal tissues. In conclusion, FZD5 expression in nasal mucosal epithelial cells is correlated with inflammatory cells and might play a role in the pathogenesis of eosinophilic CRSwNP.
Keywords
chronic rhinosinusitis; eosinophils; nasal polyp; nasal polyposis; sinusitis;
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1 Akdis, C.A., Bachert, C., Cingi, C., Dykewicz, M.S., Hellings, P.W., Naclerio, R.M., Schleimer, R.P., and Ledford, D. (2013). Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. Allergy Clin. Immunol. 131, 1479-1490.   DOI
2 Payne, S.C., Borish, L., and Steinke, J.W. (2011). Genetics and phenotyping in chronic sinusitis. J. Allergy Clin. Immunol. 128, 710-720.   DOI
3 Shah, S.A., Ishinaga, H., and Takeuchi, K. (2016). Pathogenesis of eosinophilic chronic rhinosinusitis. J. Inflamm. (Lond) 13, 11.   DOI
4 Kim, D.K., Jin, H.R., Eun, K.M., Mutusamy, S., Cho, S.H., Oh, S., and Kim, D.W. (2015). Non-eosinophilic nasal polyps shows increased epithelial proliferation and localized disease pattern in the early stage. PLoS One 10, e0139945.   DOI
5 Derycke, L., Eyerich, S., Van Crombruggen, K., Perez-Novo, C., Holtappels, G., Deruyck, N., Gevaert, P., and Bachert, C. (2014). Mixed T helper cell signatures in chronic rhinosinusitis with and without polyps. PLoS One 9, e97581.   DOI
6 Chin, D., and Harvey, R.J. (2013). Nasal polyposis: an inflammatory condition requiring effective anti-inflammatory treatment. Curr. Opin. Otolaryngol. Head Neck Surg. 21, 23-30.   DOI
7 Chen, K., Yu, Z., Yang, J., and Li, H. (2018). Expression of cysteinyl leukotriene receptor GPR17 in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps. Asian Pac. J. Allergy Immunol. 36, 93-100.
8 Yao, S., Zhu, Y., and Chen, L. (2013). Advances in targeting cell surface signalling molecules for immune modulation. Nat. Rev. Drug. Discov. 12, 130-146.   DOI
9 Doran, E., Cai, F., Holweg, C.T.J., Wong, K., Brumm, J., and Arron, J. R. (2007). Interleukin-13 in asthma and other eosinophilic disorders. Front. Med. (Lausanne) 4, 139.
10 Ponikau, J.U., Sherris, D.A., Kephart, G.M., Kern, E.B., Gaffey, T.A., Tarara, J.E., and Kita, H. (2003). Features of airway remodeling and eosinophilic inflammation in chronic rhinosinusitis: is the histopathology similar to asthma? J. Allergy Clin. Immunol. 112, 877-882.   DOI
11 Rothenberg, M.E., and Hogan, S.P. The eosinophil. Annu. Rev. Immunol. 24, 147-174.   DOI
12 Rothenberg, M.E. (1998). Eosinophilia. N. Engl. J. Med. 338, 1592-1600.   DOI
13 Rothenberg, M.E., Mishra, A., Brandt, E.B., and Hogan, S.P. (2001). Gastrointestinal eosinophils. Immunol. Rev. 179, 139-155.   DOI
14 Busche, S., Shao, X., Caron, M., Kwan, T., Allum, F., Cheung, W.A., Ge, B., Westfall, S., Simon, M.M., Barrett, A., et al. (2015). Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation. Genome Biol. 16, 290.   DOI
15 Huang, H.C., and Klein, P.S. (2004). The Frizzled family: receptors for multiple signal transduction pathways. Genome Biol. 5, 234.   DOI
16 Lin, L., Cui, L., Zhou, W., Dufort, D., Zhang, X., Cai, C.L., Bu, L., Yang, L., Martin, J., Kemler, R., et al. (2007). $\beta$-Catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis. Proc. Natl. Acad. Sci. USA 104, 9313-9318.   DOI
17 Ueno, S., Weidinger, G., Osugi, T., Kohn, A.D., Golob, J.L., Pabon, L., Reinecke, H., Moon, R.T., and Murry, C.E. (2007). Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish embryonic stem cells. Proc. Natl. Acad. Sci. USA 104, 9685-9690.   DOI
18 Peterson, Y.K., Nasarre, P., Bonilla, I.V., Hilliard, E., Samples, J., Morinelli, T.A., Hill, E.G., and Klauber-DeMore, N. (2017). Frizzled-5: a high-affinity receptor for secreted frizzled-related protein-2 activation of nuclear factor of activated T-cells c3 signaling to promote angiogenesis. Angiogenesis 20, 615-628.   DOI
19 Malbon, C.C. (2004). Frizzleds: new member of the superfamily of G-protein-coupled receptors. Front. Biosci. 9, 1048-1058.   DOI
20 Ingham, P.W., and McMahon, A.P. (2001). Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15, 2343-2360.   DOI
21 Kim, J.Y., Kim, D.K., Yu, M.S., Cha, M.J., Yu, S.L., and Kang, J. (2018). Role of epigenetics in the pathogenesis of chronic rhinosinusitis with nasal polyps. Mol. Med. Rep. 17, 1219-1227.
22 Slavin, R.G., Spector, S.L., Bernstein, I.L., Kaliner, M.A., Kennedy, D.W., Virant, F.S., Wald, E.R., Khan, D.A., Blessing-Moore, J., Lang, D.M., et al. (2005). The diagnosis and management of sinusitis: a practice parameter update. J. Allergy Clin. Immunol. 116, S13-S47.   DOI
23 North, M.L., and Ellis, A.K. (2011). The role of epigenetics in the developmental origins of allergic disease. Ann. Allergy Asthma Immunol. 106, 355-361.   DOI
24 Wu, J., Kong, W., and Yu, Y. (2010). Up-regulation of Wnt5A in chronic rhinosinusitis with nasal polyps. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 24, 1064-1067.
25 Gleich, G.J., and Adolphson, C.R. (1986). The eosinophilic leukocyte: structure and function. Adv. Immunol. 39, 177-253.   DOI
26 Sreeparvathi, A., Kalyanikuttyamma, L.K., Kumar, M., Sreekumar, N., and Veerasigamani, N. (2017). Significance of blood eosinophil count in patients with chronic rhinosinusitis with nasal polyposis. Clin. Diagn. Res. 11, MC08-11.
27 Fokkens, W.J., Lund, V.J., Mullol, J., Bachert, C., Alobid, I., Baroody, F., Cohen, N., Cervin, A., Douglas, R., Gevaert, P., et al. (2012). EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 50, 1-12.   DOI
28 Hsu, J., and Peters, A.T. (2011). Pathophysiology of chronic rhinosinusitis with nasal polyp. Am. J. Rhinol. Allergy 25, 285-90.   DOI
29 Hamilos, D. L. (2007). Chronic rhinosinusitis patterns of illness. Clin. Allergy Immunol. 20, 1-13.
30 Grgic, M.V., Cupic, H., Kalogjera, L., and Baudoin, T. (2015). Surgical treatment for nasal polyposis: predictors of outcome. Eur. Arch. Otorhinolaryngol. 272, 3735-3743.   DOI
31 Cheng, R., Sun, B., Liu, Z., Zhoa, X., Qi, L., Li, Y., and Gu, Q. (2014). Wnt5a suppresses colon cancer by inhibiting cell proliferation and epithelial-mesenchymal transition. J. Cellular Physiol. 229, 1908-1917.   DOI
32 Kuroda, J., Nakamura, M., Yoshida, M., Yamamoto, H., Maeda, T., Taniguchi, K., Nakazawa, N., Hatori, R., Ishio, A., Ozaki, A., et al. (2012). Canonical Wnt signaling in the visceral muscle is required for left-right asymmetric development of the Drosophila midgut. Mech. Dev. 128, 625-639.   DOI
33 Bo, H., Gao, L., Chen, Y., Zhang, J., and Zhu, M. (2016). Upregulation of the expression of Wnt5a promotes the proliferation of pancreatic cancer cells in vitro and in a nude mouse model. 13(2),1163-1171.   DOI