{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:03:27Z","timestamp":1792206207013,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T00:00:00Z","timestamp":1521849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R37HL068546"],"award-info":[{"award-number":["R37HL068546"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI106683"],"award-info":[{"award-number":["U19AI106683"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2018,5]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Chronic rhinosinusitis (CRS<\/jats:styled-content>) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NP<\/jats:styled-content>s). One of the features of NP<\/jats:styled-content>s is excessive fibrin deposition, which is associated with down\u2010regulation of tissue plasminogen activator (t\u2010PA<\/jats:styled-content>) in NP<\/jats:styled-content>s. As t\u2010PA<\/jats:styled-content> is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t\u2010PA<\/jats:styled-content> would be a potential new strategy for the treatment of NP<\/jats:styled-content>s.<\/jats:p><\/jats:sec>Objective<\/jats:title>The objective of this study was to determine whether short\u2010chain fatty acids (SCFA<\/jats:styled-content>s) can induce t\u2010PA<\/jats:styled-content> in airway epithelial cells via their known receptors GPR<\/jats:styled-content>41 and GPR<\/jats:styled-content>43.<\/jats:p><\/jats:sec>Methods<\/jats:title>We performed immunohistochemistry (IHC<\/jats:styled-content>) to determine whether receptors for SCFA<\/jats:styled-content>s, known as G protein\u2010coupled receptor 41\/free fatty acid receptor 3 (GPR<\/jats:styled-content>41\/FFAR<\/jats:styled-content>3) and GPR<\/jats:styled-content>43\/FFAR<\/jats:styled-content>2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE<\/jats:styled-content>) cells were stimulated with different concentrations of SCFA<\/jats:styled-content>s to test induction of t\u2010PA<\/jats:styled-content>, which was analysed by expression of mRNA<\/jats:styled-content> and protein. Mediation of responses by SCFA<\/jats:styled-content> receptors was evaluated by specific receptor gene silencing with siRNA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>Immunohistochemistry study revealed that airway epithelial cells expressed GPR<\/jats:styled-content>41 and GPR<\/jats:styled-content>43. Acetic acid, propionic acid, butyric acid and valeric acid significantly induced t\u2010PA<\/jats:styled-content> expression from two\u2010 to tenfolds. The strongest inducer of t\u2010PA<\/jats:styled-content> from NHBE<\/jats:styled-content> cells was propionic acid; cells stimulated with propionic acid released t\u2010PA<\/jats:styled-content> into the supernatant in its active form. Gene silencing of GPR<\/jats:styled-content>41 and GPR<\/jats:styled-content>43 revealed that induction of t\u2010PA<\/jats:styled-content> by SCFA<\/jats:styled-content>s was dependent upon both GPR<\/jats:styled-content>41 and GPR<\/jats:styled-content>43.<\/jats:p><\/jats:sec>Conclusions and Clinical Relevance<\/jats:title>Short\u2010chain fatty acids were shown to induce airway epithelial cell expression of t\u2010PA<\/jats:styled-content> via GPR<\/jats:styled-content>41 and GPR<\/jats:styled-content>43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13119","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T13:57:28Z","timestamp":1518443848000},"page":"544-554","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Short\u2010chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR<\/scp>41&43"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4369-3911","authenticated-orcid":false,"given":"Y.","family":"Imoto","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"},{"name":"Department of Otorhinolaryngology Head and Neck Surgery Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9144-3138","authenticated-orcid":false,"given":"A.","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Takabayashi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Sakashita","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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