{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:12:22Z","timestamp":1792807942401,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T00:00:00Z","timestamp":1714867200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>JAK inhibitors are well known for the treatment of rheumatoid arthritis (RA), but whether they can be used to treat pulmonary fibrosis, a common extra\u2010articular disease of RA, remains to be clarified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A jak2 inhibitor, CEP33779 (CEP), was administered to a rat model of RA\u2010associated interstitial lung disease to observe the degree of improvement in both joint swelling and pulmonary fibrosis. HFL1 cells were stimulated with TGF\u2010\u03b21 to observe the expression of p\u2010JAK2. Then, different concentrations of related gene inhibitors (JAK2, TGF\u03b2\u2010R1\/2, and p\u2010STAT3) or silencers (STAT3, JAK2) were administered to HFL1 cells, and the expression levels of related proteins were detected to explore the underlying mechanisms of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CEP not only reduced the degree of joint swelling and inflammation in rats but also improved lung function, inhibited the pro\u2010inflammatory factors IL\u20101\u03b2 and IL\u20106, reduced lung inflammation and collagen deposition, and alleviated lung fibrosis. CEP decreased the expression levels of TGF\u03b2\u2010R2, p\u2010SMAD, p\u2010STAT3, and ECM proteins in rat lung tissues. TGF\u2010\u03b21 induced HFL1 cells to highly express p\u2010JAK2, with the most pronounced expression at 48\u2009h. The levels of p\u2010STAT3, p\u2010SMAD3, and ECM\u2010related proteins were significantly reduced after inhibition of either JAK2 or STAT3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>JAK2 inhibitors may be an important and novel immunotherapeutic drug that can improve RA symptoms while also delaying or blocking the development of associated pulmonary fibrotic disease. The mechanism may be related to the downregulation of p\u2010STAT3 protein via inhibition of the JAK2\/STAT signaling pathway, which affects the phosphorylation of SMAD3.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.15164","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T05:38:36Z","timestamp":1714973916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>JAK2<\/scp> inhibitors improve <scp>RA<\/scp> combined with pulmonary fibrosis in rats by downregulating <scp>SMAD3<\/scp> phosphorylation"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5486-3659","authenticated-orcid":false,"given":"Yimei","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Geriatrics Chongqing Medical University  Chongqing China"},{"name":"Department Geriatrics Chongqing General Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department Geriatrics Chongqing General Hospital  Chongqing China"},{"name":"Department of Pulmonary Department of Respiratory and Critical Care Medicine Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department Geriatrics Chongqing General Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4639-3933","authenticated-orcid":false,"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department Geriatrics Chongqing General Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60008-8"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq017"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27405"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414469200"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.4081\/ejh.2021.3202"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201410-448MG"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00010904"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101436R"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-985609"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030593"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key276"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2005.12.017"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000954"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S353494"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114103"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0728-9"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2017-210728"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106748"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.478685"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.696542"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.773085"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00162.x"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152376"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126211"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34500"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmx118"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1633291100"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.07.042"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100604"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.21443"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2011.614949"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.12.3505"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxaa021"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/2397198319865367"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.15164","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T08:10:51Z","timestamp":1716797451000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185X.15164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/1756-185X.15164"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.15164","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15164"}}