{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:29:56Z","timestamp":1790501396192,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,4,26]],"date-time":"2016-04-26T00:00:00Z","timestamp":1461628800000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health, Labour, and Welfare of Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cathepsin L (<jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content>) is a lysosomal proteolytic enzyme involved in inflammation and vascular and extracellular matrix remodelling, which are the three cardinal pathological events associated with systemic sclerosis (<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c). To elucidate the potential role of <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> in the development of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c, we here investigated <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> expression in the lesional skin of patients with <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c and <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c animal models and the clinical correlation of serum <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> levels. <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> expression was elevated in dermal small vessels of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients compared with those of healthy controls. Consistently, <jats:italic><jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels were increased in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c lesional skin samples, but not in cultivated <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c dermal fibroblasts, compared with corresponding control samples from healthy individuals. Serum <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> levels were significantly higher in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients than in healthy controls and inversely correlated with skin score. Furthermore, the elevation of serum <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> levels was linked to <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c vasculopathy. Supporting these results, <jats:italic>Ctsl <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels were decreased in the skin of bleomycin\u2010treated mice, an <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c animal model recapitulating its fibrotic aspect, and <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> expression was enhanced in dermal small vessels of endothelial cell\u2010specific <jats:italic>Fli1<\/jats:italic> knockout mice, reminiscent of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c vasculopathy. Importantly, gene silencing of <jats:italic><jats:styled-content style=\"fixed-case\">FLI<\/jats:styled-content><\/jats:italic>1 induced <jats:italic><jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression and Fli1 occupied the <jats:italic><jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content><\/jats:italic> promoter in human dermal microvascular endothelial cells. Collectively, these results suggest that endothelial <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> up\u2010regulation partially due to Fli1 deficiency may contribute to the development of vasculopathy, while the decrease in dermal <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content> expression is likely associated with dermal fibrosis in SSc.<\/jats:p>","DOI":"10.1111\/exd.12920","type":"journal-article","created":{"date-parts":[[2015,12,14]],"date-time":"2015-12-14T13:18:26Z","timestamp":1450099106000},"page":"287-292","source":"Crossref","is-referenced-by-count":25,"title":["A potential contribution of altered cathepsin L expression to the development of dermal fibrosis and vasculopathy in systemic sclerosis"],"prefix":"10.1111","volume":"25","author":[{"given":"Takashi","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Tokyo Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihide","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Tokyo Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Tokyo Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Tokyo Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Saigusa","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Tokyo Graduate School of Medicine Tokyo 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