{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T22:10:35Z","timestamp":1777759835989,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874402"],"award-info":[{"award-number":["81874402"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174128"],"award-info":[{"award-number":["82174128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastric content reflux activates protease\u2010activated receptor 2 (PAR2), which is a critical step in the pathophysiological mechanisms underlying gastroesophageal reflux disease (GERD). Claudins serve as the primary constituents of tight junctions (TJs). They are in charge of the barrier and polarity of epithelial cells, and the disruption of their function can lead to chronic inflammation. The present research is designed to investigate whether PAR2 influences TJs in the development of GERD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GERD models were established both in\u00a0vivo and in\u00a0vitro. Rabeprazole and\/or GB\u201088 (a PAR2 inhibitor) were administered. The expression of PAR2, Claudin\u20101, and Claudin\u20104, M1 macrophages, transepithelial electrical resistance (TEER), Interleukin\u20108 (IL\u20108), and Interleukin\u20101\u03b2 (IL\u20101\u03b2) were measured. Furthermore, cells were treated with SLIGKV\u2010NH2 (a PAR2 agonist) and GB\u201088 to verify the impact of PAR2 on TJs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Rabeprazole improved pathological changes, decreased the concentration of IL\u20108 and IL\u20101\u03b2, and inhibited the accumulation of M1 macrophages in GERD rats. Rabeprazole inhibited the expression of PAR2 and enhanced Claudin\u20101 and Claudin\u20104 in\u00a0vivo. GB\u201088 declined PAR2 and the concentration of IL\u20108 and IL\u20101\u03b2, and increased Claudin\u20101, Claudin\u20104, and TEER in\u00a0vitro. The combination of GB\u201088 and rabeprazole was more effective in restoring Claudin\u20104.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In GERD, elevated PAR2 expression impaired esophageal mucosal barrier function by downregulating and inducing the redistribution of Claudin\u20101 and Claudin\u20104, while promoting M1 macrophage\u2010mediated secretion of IL\u20108 and IL\u20101\u03b2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70291","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:39:36Z","timestamp":1777264776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of\n                    <scp>PAR2<\/scp>\n                    on Tight Junctions and Esophageal Mucosal Inflammation in Rats with Gastroesophageal Reflux Disease"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7658-7104","authenticated-orcid":false,"given":"Mengdie","family":"Du","sequence":"first","affiliation":[{"name":"Shanghai Municipal Hospital of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luye","family":"Wang","sequence":"additional","affiliation":[{"name":"Hepatology Department of integrated Chinese and Western medicine Nantong Third People's Hospital  Nantong China"},{"name":"Hepatology Department of integrated Chinese and Western medicine Affiliated Nantong Hospital 3 of Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqian","family":"Duan","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Hospital of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Hospital of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenshang","family":"Fu","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Hospital of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6410-3004","authenticated-orcid":false,"given":"Yongshun","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Hospital of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-313589"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2074535"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/000313481808400651"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13104"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-019-01572-y"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i29.4750"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.02943.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-021-00609-w"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091425"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2013.06.003"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2005.08.003"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00454.2011"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-005-1628-6"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-44466-z"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2012.tb00450.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7268-7"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2013.828772"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.272"},{"key":"e_1_2_11_20_1","first-page":"5386","article-title":"Chronic Stress Augments Esophageal Inflammation, and Alters the Expression of Transient Receptor Potential Vanilloid 1 and Protease\u2010Activated Receptor 2 in a Murine Model","volume":"19","author":"Wulamu W.","year":"2019","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.265"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl16600"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156251"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0462-y"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(91)90003-4"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000130"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000508661"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000486480"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020569"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/1945892420932486"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm17012"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-021-01424-z"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14299"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-014-0164-8"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.09.047"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032502"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00374.2014"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011874"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28260"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13056"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305533"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00333.2014"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm.2010.16.4.374"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00385.2005"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-021-06980-w"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2022.2132534"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00365.2020"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117066"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13841"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05878-1"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.03.004"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.02.005"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.70291","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nmo.70291","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.70291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:44:05Z","timestamp":1777470245000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.70291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/nmo.70291"],"URL":"https:\/\/doi.org\/10.1111\/nmo.70291","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70291"}}