{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:57:07Z","timestamp":1780498627014,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["16ZR1426100"],"award-info":[{"award-number":["16ZR1426100"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) has not been fully elucidated. This study sought to explore the role and mechanism of transient receptor potential canonical channel 6 (TRPC6) in the pathogenesis of CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemistry (IHC) was employed to evaluate TRPC6 immunolabeling. Real\u2010time polymerase chain reaction (PCR) was conducted to assay TRPC6, stromal interaction molecule 1 (STIM1), and calcium release\u2010activated calcium channel protein 1 (Orai1) messenger RNA (mRNA) levels in 70 patients with CRSwNP, including eosinophilic CRSwNP (ECRSwNP) or non\u2010eosinophilic CRSwNP (nECRSwNP), and 28 control subjects. The concentrations of inflammatory mediators, including interleukin (IL)\u20101\u03b2, IL\u20105, and IL\u201025, were assayed by enzyme\u2010linked immunosorbent assay (ELISA). In experiments on human nasal epithelial cell (HNEC) culture and stimulation, the mean fluorescence intensity (MFI) of intracellular Ca<jats:sup>2+<\/jats:sup> was assayed by flow cytometry. Western blotting, real\u2010time PCR, and ELISA were also conducted to assess the effects and mechanisms of TRPC6 activator 1\u2010oleoyl\u20102\u2010acetyl\u2010glycerol (OAG) and TRPC6 inhibitor 1\u2010[2\u2010(4\u2010methoxyphenyl)\u20102\u2010[3\u2010(4\u2010methoxyphenyl) propoxy]ethyl\u20101H\u2010imidazole (SKF\u201096365) on HNECs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Upregulation of TRPC6, STIM1, and Orai1 levels was found in CRSwNP patients, particularly in those with ECRSwNP. TRPC6\u2010positive cells correlated positively with the numbers of eosinophils and neutrophils, respectively. Moreover, TRPC6 mRNA was positively correlated with STIM1 and Orai1 mRNA levels. The concentrations of inflammatory mediators, including IL\u20101\u03b2, IL\u20105, and IL\u201025, were elevated in CRSwNP, especially in ECRSwNP. In cultured HNECs, TRPC6, STIM1, Orai1, Ca<jats:sup>2+<\/jats:sup> MFI levels, and inflammatory mediators were upregulated by lipopolysaccharide (LPS) and OAG but were inhibited by SKF\u201096365.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TRPC6 plays a pro\u2010inflammatory role in the pathogenesis of CRSwNP via regulating Ca<jats:sup>2+<\/jats:sup> flow.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22208","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T08:06:30Z","timestamp":1537085190000},"page":"1334-1341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pro\u2010inflammatory role of transient receptor potential canonical channel 6 in the pathogenesis of chronic rhinosinusitis with nasal polyps"],"prefix":"10.1002","volume":"8","author":[{"given":"Ru","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Xian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai 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Otolaryngology\u2013Head and Neck Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21871"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2016.05.004"},{"issue":"1","key":"e_1_2_6_4_1","first-page":"S3","article-title":"International Consensus Statement on Allergy and Rhinology: Rhinosinusitis Executive Summary","volume":"6","author":"Orlandi RR","year":"2016","journal-title":"Int Forum Allergy 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