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ID 53117
JaLCDOI
フルテキストURL
Thumnail 69_1_1.pdf 5.17 MB
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
Sakai, Yoshiki ONO Pharmaceutical Co., Ltd.
Tanabe, Katsuyuki Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Makino, Hirofumi Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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.
キーワード
prostacyclin
ONO-1301
diabetic nephropathy
TGF-β1
diabetes mellitus
Amo Type
Original Article
発行日
2015-02
出版物タイトル
Acta Medica Okayama
69巻
1号
出版者
Okayama University Medical School
開始ページ
1
終了ページ
15
ISSN
0386-300X
NCID
AA00508441
資料タイプ
学術雑誌論文
言語
English
著作権者
CopyrightⒸ 2015 by Okayama University Medical School
論文のバージョン
publisher
査読
有り
PubMed ID
Web of Sience KeyUT
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/53128