{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:59:18Z","timestamp":1777535958876,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T00:00:00Z","timestamp":1538092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773464, 81441090"],"award-info":[{"award-number":["81773464, 81441090"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["1708085MH195"],"award-info":[{"award-number":["1708085MH195"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Exogenous H<jats:sub>2<\/jats:sub>S donor, sodium hydrosulfide (NaHS), can influence the bleomycin\u2010induced pulmonary fibrosis by attenuating the epithelial\u2010mesenchymal transition (EMT) of alveolar epithelial cells, but whether NaHS affects paraquat (PQ)\u2010induced EMT and the molecular mechanisms remain unclarified. The aim of the present study is to examine the effect of exogenous NaHS on PQ\u2010induced EMT in human alveolar epithelial cells (A549 cells) and assess if this effect occurs through regulating transforming growth factor (TGF)\u2010\u03b21\/Smad2\/3 signaling pathway. The expressions of endogenous H<jats:sub>2<\/jats:sub>S producing enzymes, namely cystathionine \u03b2\u2010synthase, cystathionine \u03b3\u2010lyase and 3\u2010mercaptopyruvate sulfur transferase, were detected by reverse transcription\u2010polymerase chain reaction and western blotting. The induced EMT was assessed by morphological and phenotypic characterizations, and the protein level of E\u2010cadherin and vimentin were detected by western blotting. To investigate the effect of NaHS on PQ\u2010induced EMT and potential mechanism, A549 cells were pretreated with NaHS before incubating with PQ and then evaluated by morphological changes, cell migration ability, the expression of EMT markers and TGF\u2010\u03b21\/Smad2\/3 signaling pathway related proteins. PQ significantly downregulated the expression levels of cystathionine \u03b2\u2010synthase and cystathionine \u03b3\u2010lyase, but not 3\u2010mercaptopyruvate sulfur transferase, in a time\u2010dependent manner in A549 cells. Exogenous NaHS could significantly retard PQ\u2010induced morphological changes and cell migration ability. Furthermore, exogenous NaHS significantly upregulated the expression of E\u2010cadherin, whereas it downregulated the expression of vimentin. In addition, exogenous NaHS could also significantly attenuates PQ\u2010induced TGF\u2010\u03b21, phosphorylated Smad2\/3 proteins expression, which induced by PQ in a time\u2010dependent manner. This study provides the first evidence that exogenous NaHS attenuates PQ\u2010induced EMT and migration of human alveolar epithelial cells through regulating the TGF\u2010\u03b21\/Smad2\/3 signaling pathway.<\/jats:p>","DOI":"10.1002\/jat.3734","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T19:07:33Z","timestamp":1538161653000},"page":"432-440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Hydrogen sulfide attenuates paraquat\u2010induced epithelial\u2010mesenchymal transition of human alveolar epithelial cells through regulating transforming growth factor\u2010\u03b21\/Smad2\/3 signaling pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"You\u2010Wei","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University  Hefei Anhui 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng\u2010Juan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University  Hefei Anhui 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da\u2010Long","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University  Hefei Anhui 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng\u2010Ping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University  Hefei Anhui 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-0421","authenticated-orcid":false,"given":"Cheng\u2010Fan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University  Hefei Anhui 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University  Hefei Anhui 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.11.019"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2882"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2737"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408440701669959"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y09-039"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2007.04.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.08.017"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.4454"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0063OC"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.1938"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605669103"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-010-0510-x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5309"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jflm.2018.03.007"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5289"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6813"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2016.1257433"},{"key":"e_1_2_7_20_1","first-page":"1781","article-title":"Hydrogen sulfide alleviates myocardial fibrosis in mice with alcoholic cardiomyopathy by downregulating autophagy","volume":"40","author":"Liang B.","year":"2017","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_7_21_1","first-page":"1867","article-title":"Hydrogen sulfide attenuates myocardial fibrosis in diabetic rats through the JAK\/STAT signaling pathway","volume":"41","author":"Liu M.","year":"2018","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000441504"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2014.02.006"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.5.2896"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.028"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/1872213X07666131229131451"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/458720"},{"key":"e_1_2_7_28_1","first-page":"1597","article-title":"Advances in the mechanism of paraquat\u2010induced pulmonary injury","volume":"20","author":"Sun B.","year":"2016","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.09.003"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-016-2774-4"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2015.09.010"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.5"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2013.834361"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120192"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.3734","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.3734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:53:10Z","timestamp":1760554390000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.3734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,28]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1002\/jat.3734"],"URL":"https:\/\/doi.org\/10.1002\/jat.3734","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,28]]},"assertion":[{"value":"2018-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}