{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T11:15:50Z","timestamp":1774869350669,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,1,7]],"date-time":"2018-01-07T00:00:00Z","timestamp":1515283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Foundation of Outstand Young of the First Peoples' Hospital of Chenzhou","award":["N2014-007"],"award-info":[{"award-number":["N2014-007"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To determine whether pirfenidone attenuates lung fibrosis by interfering with the hedgehog (Hh) signalling pathway in patients with systemic sclerosis\u2010associated interstitial lung disease (<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c\u2010<jats:styled-content style=\"fixed-case\">ILD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010five <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c\u2010<jats:styled-content style=\"fixed-case\">ILD<\/jats:styled-content> patients (20 first visit, five who underwent pirfenidone treatment for 6 months) and 10 healthy controls were recruited. Lung tissues were obtained by open\u2010chest surgery, and primary lung fibroblasts were isolated, cultured and stimulated with pirfenidone. The levels of the proteins glioma\u2010associated oncogene 1 (<jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>1), suppressor of fused (Sufu), \u03b1\u2010smooth muscle actin, and fibronectin in lung tissues or fibroblasts were determined by Western blotting. The messenger <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels of <jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>1, glioma\u2010associated oncogene 2, protein patched homolog 1, and Sufu in lung tissues or fibroblasts were determined by quantitative reverse\u2010transcription polymerase chain reaction. Meanwhile, the levels of phosphorylation glycogen synthase kinasep\u20103\u03b2 (<jats:styled-content style=\"fixed-case\">pGSK<\/jats:styled-content>\u20103\u03b2), phosphorylation <jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content>2 (<jats:styled-content style=\"fixed-case\">pSMAD<\/jats:styled-content>2), and phosphorylation c\u2010Jun N\u2010terminal kinase (p<jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>) in fibroblasts were determined by Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hh pathway activation was increased in the lung tissue of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c\u2010<jats:styled-content style=\"fixed-case\">ILD<\/jats:styled-content> patients and was decreased by pirfenidone, Sufu was upregulated in lung fibroblasts isolated from <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c\u2010<jats:styled-content style=\"fixed-case\">ILD<\/jats:styled-content> patients after pirfenidone challenge, and pirfenidone inhibited the phosphorylation of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103\u03b2 signalling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pirfenidone has anti\u2010fibrotic effects in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c\u2010<jats:styled-content style=\"fixed-case\">ILD<\/jats:styled-content> patients by interfering with both the Hh signalling pathway and the <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103\u03b2 signalling pathway via the regulation of Sufu expression. These results might promote its use in other Hh driven lung diseases such as idiopathic pulmonary fibrosis and especially the interstitial lung disease associated with connective tissue diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.13247","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T05:16:26Z","timestamp":1515561386000},"page":"477-486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Anti\u2010fibrotic effects of pirfenidone by interference with the hedgehog signalling pathway in patients with systemic sclerosis\u2010associated interstitial lung disease"],"prefix":"10.1111","volume":"21","author":[{"given":"Hua","family":"Xiao","sequence":"first","affiliation":[{"name":"Southern Medical University Guangzhou China"},{"name":"Department of Rheumatology Guangdong General Hospital Guangdong Academy of Medical Sciences Guangzhou China"},{"name":"Department of 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