{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:48:34Z","timestamp":1785739714390,"version":"3.56.0"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"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":["82003363"],"award-info":[{"award-number":["82003363"]}],"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":["82073449"],"award-info":[{"award-number":["82073449"]}],"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":["82203930"],"award-info":[{"award-number":["82203930"]}],"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":["82203932"],"award-info":[{"award-number":["82203932"]}],"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":["82304024"],"award-info":[{"award-number":["82304024"]}],"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":["82373486"],"award-info":[{"award-number":["82373486"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","award":["2022ZZTS061"],"award-info":[{"award-number":["2022ZZTS061"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010083","name":"Hunan Provincial Innovation Foundation for Postgraduate","doi-asserted-by":"publisher","award":["CX20220343"],"award-info":[{"award-number":["CX20220343"]}],"id":[{"id":"10.13039\/501100010083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019081","name":"Science and Technology Program of Hunan Province","doi-asserted-by":"publisher","award":["2022RC1216"],"award-info":[{"award-number":["2022RC1216"]}],"id":[{"id":"10.13039\/501100019081","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The cystathionine \u03b3\u2010lyase (CSE)\/hydrogen sulfide (H\n                      <jats:sub>2<\/jats:sub>\n                      S) axis has emerged as a key regulator in tissue fibrogenesis. This study aimed to explore the role of the CSE\/H\n                      <jats:sub>2<\/jats:sub>\n                      S axis in systemic sclerosis (SSc) and to investigate its underlying mechanisms to identify promising therapeutic targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CSE\/H\n                      <jats:sub>2<\/jats:sub>\n                      S levels were assessed in serum samples from 25 patients with SSc and 28 healthy controls. Human dermal fibroblasts from patients with SSc and healthy controls were used for functional studies, including propargylglycine (CSE inhibitor) treatment, Gyy4137, a slow\u2010releasing hydrogen sulfide donor, CSE silencing, and CSE overexpression, combined with liquid chromatography\u2013tandem mass spectrometry (LC\u2010MS\/MS)\u2013based S\u2010sulfhydration proteomics. Molecular dynamics simulations were performed to study the effects of S\u2010sulfhydration on protein structure, and an Smad3 C121S (cysteine [Cys] 121 mutated to Ser) mutant was generated to verify the function targets of S\u2010sulfhydration. In vivo, bleomycin\u2010induced mouse models of skin and lung fibrosis were constructed to evaluate the effects of CSE overexpression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In human samples, CSE\/H\n                      <jats:sub>2<\/jats:sub>\n                      S levels were reduced in SSc. CSE inhibition promoted extracellular matrix deposition. S\u2010sulfhydration proteomics showed that S\u2010sulfhydration levels were globally reduced in SSc compared to controls. CSE overexpression increased S\u2010sulfhydration on Smad3, suppressed transforming growth factor \u03b2 1 (TGF\u03b21)\/Smad3 signaling, mitigating skin fibrosis. Notably, Cys121 on Smad3, identified as a pivotal target for S\u2010sulfhydration by proteomics, was shown to fine\u2010tune its MH1 domain, with its mutation impairing the antifibrotic effects. In mice, CSE overexpression attenuated bleomycin\u2010induced skin and lung fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Smad3 S\u2010sulfhydration mediates the antifibrotic effect of CSE in SSc, highlighting it as a critical mechanism and promising therapeutic target.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70085-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70085","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T09:12:45Z","timestamp":1770628365000},"page":"1741-1754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cystathionine \u03b3\u2010Lyase\u2010Dependent S\u2010Sulfhydration of Smad3: A Novel Target to Alleviate Fibrosis in Systemic Sclerosis"],"prefix":"10.1002","volume":"78","author":[{"given":"Jiani","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangfan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Pi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuotong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6214-8057","authenticated-orcid":false,"given":"Rong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.10.065"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac363"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/kjm2.12505"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-226336"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01032-1"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-021-08889-8"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30529"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2024.2323528"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2020.02.003"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00741-6"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.5133"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2020.05.010"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000000537"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3391"},{"key":"e_1_2_6_17_1","first-page":"8608","article-title":"H2S\u2010induced sulfhydration: biological function and detection methodology","author":"Zhang D","year":"2017","journal-title":"Front Pharmacol"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31247"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.062743"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-016-2774-4"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.12642"},{"issue":"2","key":"e_1_2_6_22_1","first-page":"298","article-title":"Homocysteine plasma concentration is related to severity of lung impairment in scleroderma","volume":"30","author":"Caramaschi P","year":"2003","journal-title":"J Rheumatol"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101898"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204424"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106886"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106057"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.03.076"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05889-8"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.2144\/000112729"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00028.2021"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2014.11.014"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2018.07.008"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022079"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2269"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101817"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103038"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.18088"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105119"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2024.01.004"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2023.127366"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22081334"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022111"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.3.999"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.003469"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00766-7"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.14240"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202012097"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06997-9"},{"key":"e_1_2_6_50_1","first-page":"tkad024","article-title":"S\u2010nitrosylation\u2010mediated coupling of DJ\u20101 with PTEN induces PI3K\/AKT\/mTOR pathway\u2010dependent keloid formation. Burns","volume":"11","author":"Lv D","year":"2023","journal-title":"Trauma"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102812"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.06.038"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70085","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.70085","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70085","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:39:13Z","timestamp":1785739153000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,22]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/art.70085"],"URL":"https:\/\/doi.org\/10.1002\/art.70085","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,22]]},"assertion":[{"value":"2025-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}