{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:43:18Z","timestamp":1789990998316,"version":"4.0.1"},"reference-count":64,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,1,12]],"date-time":"2012-01-12T00:00:00Z","timestamp":1326326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010647","name":"Canadian Thoracic Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010647","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>\n                    Asthma is a chronic inflammatory disease that is associated with airway remodeling, including hyperplasia of airway epithelial cells and airway smooth muscle cells, and goblet cell differentiation. We wished to address the potential role of histamine, a key biogenic amine involved in allergic reactions, in airway remodeling through the epidermal growth factor receptor (EGFR) pathway. Here, we demonstrate that histamine releases 2 EGFR ligands, amphiregulin and heparin\u2010binding epidermal growth factor\u2010like growth factor (HB\u2010EGF), from airway epithelial cells. Amphiregulin and HB\u2010EGF were expressed in airway epithelium of patients with asthma. Histamine up\u2010regulated their mRNA expression (amphiregulin 3.2\u2010fold,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001; HB\u2010EGF 2.3\u2010fold,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) and triggered their release (amphiregulin EC\n                    <jats:sub>50<\/jats:sub>\n                    0.50 \u03bcM, 31.2\u00b12.7 pg\/ml with 10 \u03bcM histamine,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01; HB\u2010EGF EC\n                    <jats:sub>50<\/jats:sub>\n                    0.54 \u03bcM, 78.5\u00b11.8 pg\/ml with 10 \u03bcM histamine,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001) compared to vehicle control (amphiregulin 19.3\u00b10.9 pg\/ ml; HB\u2010EGF 60.2\u00b1 1.0 pg\/ml), in airway epithelial cells. Histamine increased EGFR phosphorylation (2.1\u2010fold by Western blot analysis) and induced goblet cell differentiation (CLCA1 up\u2010regulation by real\u2010time qPCR) in normal human bronchial epithelial (NHBE) cells. Moreover, amphiregulin and HB\u2010EGF caused proliferation and migration of both NHBE cells and human airway smooth muscle cells. These results suggest that histamine may induce airway remodeling\n                    <jats:italic>via<\/jats:italic>\n                    the epithelial\u2010derived EGFR ligands amphiregulin and HB\u2010EGF.\u2014Hirota, N., Risse, P.\u2010A., Novali, M., McGovern, T., Al\u2010Alwan, L., McCuaig, S., Proud, D., Hayden, P., Hamid, Q., Martin, J. G. Histamine may induce airway remodeling through release of epidermal growth factor receptor ligands from bronchial epithelial cells.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 1704\u20101716 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-197061","type":"journal-article","created":{"date-parts":[[2012,1,13]],"date-time":"2012-01-13T01:32:41Z","timestamp":1326418361000},"page":"1704-1716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Histamine may induce airway remodeling through release of epidermal growth factor receptor ligands from bronchial epithelial cells"],"prefix":"10.1096","volume":"26","author":[{"given":"Nobuaki","family":"Hirota","sequence":"first","affiliation":[{"name":"Meakins\u2010Christie Laboratories Department of Medicine McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul\u2010Andre","family":"Risse","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories Department of Medicine McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Novali","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories Department of Medicine McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby","family":"McGovern","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories Department of Medicine McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Al\u2010Alwan","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories Department of Medicine McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"McCuaig","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories Department of Medicine McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Proud","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Faculty of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hayden","sequence":"additional","affiliation":[{"name":"MatTek Corporation Ashland Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qutayba","family":"Hamid","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories Department of Medicine McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Martin","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories Department of Medicine McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00019810"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200607-1062OC"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012705"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.02.039"},{"key":"e_1_2_7_6_1","first-page":"L365","article-title":"Histamine stimulates proliferation of airway smooth muscle and induces c\u2010fos expression","volume":"259","author":"Panettieri R. 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