ONO-1301, a Sustained-Release Prostacyclin Analog, Ameliorates the Renal Alterations in a Mouse Type 2 Diabetes Model Possibly Through Its Protective Effects on Mesangial Cells
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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.
収録刊行物
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- Acta Medica Okayama
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Acta Medica Okayama 69 (1), 1-15, 2015-02
Okayama University Medical School
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詳細情報 詳細情報について
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- CRID
- 1390009224819383168
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- NII論文ID
- 120005549937
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- NII書誌ID
- AA00508441
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- ISSN
- 0386300X
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- PubMed
- 25703166
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- IRDB
- PubMed
- CiNii Articles