JaLCDOI 10.18926/AMO/53117
フルテキストURL 69_1_1.pdf
著者 Watatani, Hiroyuki| Yamasaki, Hiroko| Maeshima, Yohei| Nasu, Tatsuyo| Hinamoto, Norikazu| Ujike, Haruyo| Sugiyama, Hitoshi| Sakai, Yoshiki| Tanabe, Katsuyuki| Makino, Hirofumi|
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 25703166
Web of Sience KeyUT 000349740300001
関連URL http://ousar.lib.okayama-u.ac.jp/metadata/53128