ID | 53117 |
JaLCDOI | |
フルテキストURL | |
著者 |
Watatani, Hiroyuki
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamasaki, Hiroko
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Maeshima, Yohei
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nasu, Tatsuyo
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hinamoto, Norikazu
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ujike, Haruyo
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sugiyama, Hitoshi
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Sakai, Yoshiki
ONO Pharmaceutical Co., Ltd.
Tanabe, Katsuyuki
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
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Makino, Hirofumi
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | Diabetic nephropathy is the most common pathological disorder predisposing patients to end-stage renal disease. Considering the increasing prevalence of type 2 diabetes mellitus worldwide, novel therapeutic approaches are urgently needed. ONO-1301 is a novel sustained-release prostacyclin analog that inhibits thromboxane A2 synthase. Here we examined the therapeutic effects of the intermittent administration of slow-release ONO-1301 (SR-ONO) on diabetic nephropathy in obese type 2 diabetes mice, as well as its direct effects on mesangial cells. The subcutaneous injection of SR-ONO (3mg/kg) every 3 wks did not affect the obesity or hyperglycemia in the db/db obese mice used as a model of type 2 diabetes, but it significantly ameliorated their albuminuria, glomerular hypertrophy, glomerular accumulation of type IV collagen, and monocyte/macrophage infiltration, and also the increase of TGF-β1, α-smooth muscle actin (α-SMA) and MCP-1 compared to vehicle treatment. In cultured mouse mesangial cells, ONO-1301 concentration-dependently suppressed the increases in TGF-β, type IV collagen, α-SMA, MCP-1 and fibronectin induced by high ambient glucose, at least partly through prostacyclin (PGI2) receptor-mediated signaling. Taken together, these results suggest the potential therapeutic efficacy of the intermittent administration of SR-ONO against type 2 diabetic nephropathy, possibly through protective effects on mesangial cells.
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キーワード | prostacyclin
ONO-1301
diabetic nephropathy
TGF-β1
diabetes mellitus
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Amo Type | Original Article
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出版物タイトル |
Acta Medica Okayama
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発行日 | 2015-02
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巻 | 69巻
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号 | 1号
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出版者 | Okayama University Medical School
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開始ページ | 1
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終了ページ | 15
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ISSN | 0386-300X
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NCID | AA00508441
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資料タイプ |
学術雑誌論文
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言語 |
英語
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著作権者 | CopyrightⒸ 2015 by Okayama University Medical School
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論文のバージョン | publisher
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査読 |
有り
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PubMed ID | |
Web of Science KeyUT | |
関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/53128
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