{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:07Z","timestamp":1787013967178,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004946","name":"National Chung-Hsing University","doi-asserted-by":"publisher","award":["NCHU108ST001F"],"award-info":[{"award-number":["NCHU108ST001F"]}],"id":[{"id":"10.13039\/501100004946","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST\u2010104\u20102320\u2010B\u2010005\u2010002\u2010MY3"],"award-info":[{"award-number":["MOST\u2010104\u20102320\u2010B\u2010005\u2010002\u2010MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST\u2010106\u20102320\u2010B\u2010005\u2010001\u2010MY3"],"award-info":[{"award-number":["MOST\u2010106\u20102320\u2010B\u2010005\u2010001\u2010MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veterans General Hospital","doi-asserted-by":"publisher","award":["TCVGH\u20101077311C"],"award-info":[{"award-number":["TCVGH\u20101077311C"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veterans General Hospital","doi-asserted-by":"publisher","award":["TCVGH\u20101077329D"],"award-info":[{"award-number":["TCVGH\u20101077329D"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veterans General Hospital","doi-asserted-by":"publisher","award":["TCVGH\u20101087308C"],"award-info":[{"award-number":["TCVGH\u20101087308C"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010101","name":"Taichung Veterans General Hospital","doi-asserted-by":"publisher","award":["TCVGH\u20101087327D"],"award-info":[{"award-number":["TCVGH\u20101087327D"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Idiopathic pulmonary fibrosis is a devastating disease with multiple contributing factors. Insulin\u2010like growth factor 1 receptor (IGF1R), with a reciprocal function to aryl hydrocarbon receptor (AhR), is involved in airway inflammation. The exact relationship between IGF1R and AhR in lung fibrogenesis is unclear. This study aimed to investigate the cascade pathway involving IGF1R and AhR in idiopathic pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The AhR and IGF1R expressions were determined in the lungs of idiopathic pulmonary fibrosis patients and in a rodent fibrosis model. Pulmonary fibrosis was evaluated in bleomycin (BLM)\u2010induced lung injury in wild type and AhR knockout (\n                      <jats:italic>Ahr<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice. The effects of IGF1R inhibition and AhR activation\n                      <jats:italic>in vitro<\/jats:italic>\n                      on TGF\u2010\u03b21\u2010induced epithelial\u2013mesenchymal transition (EMT) in Beas2B cells and\n                      <jats:italic>in vivo<\/jats:italic>\n                      on BLM\u2010exposed mice were also examined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>There were increased IGF1R levels but AhR expression decreased in the lung of idiopathic pulmonary fibrosis patients and BLM\u2010induced mice. Knockout of AhR aggravated lung fibrosis, while the use of IGF1R inhibitor and AhR agonist significantly attenuated such effects and inhibited TGF\u2010\u03b21\u2010induced epithelial\u2013mesenchymal transition in Beas2B cells. Both TGF\u2010\u03b21 and BLM markedly suppressed AhR expression through endoplasmic reticulum stress and consequently, IGF1R activation. The IGF1R inhibitor and specific knockdown of IGF1R reversed the activation of the TGF\u2010\u03b21 signal pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>In the development of idiopathic pulmonary fibrosis, AhR and IGF1R play opposite roles via the TGF\u2010\u03b2\/Smad\/STAT signalling cascade. The AhR\/IGF1R axis is a potential target for the treatment of lung injury and fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15806","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T20:39:42Z","timestamp":1643229582000},"page":"3430-3451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Aggravation of pulmonary fibrosis after knocking down the aryl hydrocarbon receptor in the insulin\u2010like growth factor 1 receptor pathway"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8569-5280","authenticated-orcid":false,"given":"Sheng\u2010Mao","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaw\u2010Ji","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology &amp; Rheumatology, Department of Internal Medicine Asia University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Chuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Taichung Veterans General Hospital  Taichung Taiwan"},{"name":"Department of Medical Research Taichung Veterans General Hospital  Taichung Taiwan"},{"name":"Ph.D. Program in Translational Medicine, Rong Hsing Research Center for Translational Medicine National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack L.","family":"Arbiser","sequence":"additional","affiliation":[{"name":"Department of Dermatology Emory University School of Medicine, Winship Cancer Institute, Atlanta Veterans Administration Health Center  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5011-0206","authenticated-orcid":false,"given":"Leonardo","family":"Elia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine University of Brescia  Brescia Lombardia Italy"},{"name":"Humanitas Clinical and Research Center IRCCS  Rozzano Lombardia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0431-1282","authenticated-orcid":false,"given":"Meei\u2010Ling","family":"Sheu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences National Chung Hsing University  Taichung Taiwan"},{"name":"Department of Medical Research Taichung Veterans General Hospital  Taichung Taiwan"},{"name":"Ph.D. Program in Translational Medicine, Rong Hsing Research Center for Translational Medicine National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15537"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.03.046"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1193"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.31.3.1"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-013-0391-7"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200808-089RM"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0857-1"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000327499"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.158"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2020.12.035"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2004.00397.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau2814"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02006"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.21.022404.142018"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7732381"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.3.9606031"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14612-5"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15285"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-019-1093-z"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-019-0994-4"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci20530"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.8.1.7512194"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2012.02837.x"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402582"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2307"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.231035"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0876-y"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/BPH.15178"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-14-101"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00069307"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3434"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.08.011"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201001-0014OC"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1201-y"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343301"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1386-6346(99)00068-6"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04561-4"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0445OC"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402584"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01117"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2015.00012"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55040083"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115909"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920011795016818"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2010.04257.x"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-020-2112-7"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00410.2011"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.11.011"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci125366"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm200005043421806"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00163.2007"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2005.07.006"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8600"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2020.02.009"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.328"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-019-0361-3"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097266"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15806","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.15806","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15806","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T03:22:54Z","timestamp":1780975374000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.15806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,28]]},"references-count":60,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/bph.15806"],"URL":"https:\/\/doi.org\/10.1111\/bph.15806","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,28]]},"assertion":[{"value":"2021-05-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}