{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:23:49Z","timestamp":1791062629065,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The study of lysophosphatidic acid (<jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content>) receptor has recently focused on its involvement in the pathogenesis of systemic sclerosis (<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c). We examined the inhibitory effects of the antagonist for the <jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content> receptor, a selective <jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content><jats:sub>1<\/jats:sub> and <jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content><jats:sub>3<\/jats:sub> antagonist (Ki16425), on dermal and lung fibrosis in a mouse model of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. Ki16425 was administered intra\u2010dermally after 6\u00a0h on the same sites as bleomycin injection. Histopathological examination showed that skin lesions were markedly attenuated by treatment with Ki16425 at doses of 1 and 10\u00a0mg\/kg, along with reduced dermal thickness. Hydroxyproline contents in the Ki16425\u2010treated skin showed a decrease of 35% (1\u00a0mg\/kg) and 45% (10\u00a0mg\/kg) compared with those in the oil\u2010injected skin of the controls. The number of mast cells and phospho\u2010Smad2\/3\u2010positive spindle cells of the Ki16425\u2010treated skin was significantly decreased compared with that in the controls. Additionally, <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> analysis showed that the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010<jats:italic>\u03b2<\/jats:italic>1, <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> MIP<\/jats:styled-content>\u20101<jats:italic>\u03b1<\/jats:italic>,<jats:styled-content style=\"fixed-case\"> IFN<\/jats:styled-content>\u2010<jats:italic>\u03b3<\/jats:italic> and collagen <jats:italic>\u03b1<\/jats:italic>1(I) were significantly decreased in both the 1\u2010mg\/kg and 10\u2010mg\/kg groups of the Ki16425\u2010treated mice compared with those in the controls. Furthermore, treatment with bleomycin and Ki16425 showed reduction in lung fibrosis, and the hydroxyproline contents in the lungs of the Ki16425\u2010treated mice showed a decrease of 25% (1\u00a0mg\/kg) and 32% (10\u00a0mg\/kg) compared with those in the lungs of the controls. Taken together, Ki16425 was found to improve dermal and lung fibrosis in a mouse model of bleomycin\u2010induced murine scleroderma. These results suggest that Ki16425 has the potential to be an effective new treatment for scleroderma.<\/jats:p>","DOI":"10.1111\/exd.12752","type":"journal-article","created":{"date-parts":[[2015,5,9]],"date-time":"2015-05-09T02:33:03Z","timestamp":1431138783000},"page":"698-702","source":"Crossref","is-referenced-by-count":46,"title":["Antifibrotic effect of lysophosphatidic acid receptors <scp>LPA<\/scp><sub>1<\/sub> and <scp>LPA<\/scp><sub>3<\/sub> antagonist on experimental murine scleroderma induced by bleomycin"],"prefix":"10.1111","volume":"24","author":[{"given":"Takenobu","family":"Ohashi","sequence":"first","affiliation":[{"name":"Department of Dermatology Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology Fukushima Medical University Fukushima 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