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ID 53117
JaLCDOI
FullText URL
Thumnail 69_1_1.pdf 5.17 MB
Author
Watatani, Hiroyuki
Yamasaki, Hiroko
Maeshima, Yohei
Nasu, Tatsuyo
Hinamoto, Norikazu
Ujike, Haruyo
Sakai, Yoshiki
Abstract
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.
Keywords
prostacyclin
ONO-1301
diabetic nephropathy
TGF-β1
diabetes mellitus
Amo Type
Original Article
Published Date
2015-02
Publication Title
Acta Medica Okayama
Volume
volume69
Issue
issue1
Publisher
Okayama University Medical School
Start Page
1
End Page
15
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
Copyright Holders
CopyrightⒸ 2015 by Okayama University Medical School
File Version
publisher
Refereed
True
PubMed ID
Web of Sience KeyUT
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/53128