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
| Autor: | Watatani, Hiroyuki, Yamasaki, Hiroko, Maeshima, Yohei, Nasu, Tatsuyo, Hinamoto, Norikazu, Ujike, Haruyo, Sugiyama, Hitoshi, Sakai, Yoshiki, Tanabe, Katsuyuki, Makino, Hirofumi |
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| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Collagen Type IV Male prostacyclin Pyridines Tumor Necrosis Factor-alpha diabetic nephropathy Lipids Actins Disease Models Animal Mice Oxidative Stress Diabetes Mellitus Type 2 TGF-β1 Delayed-Action Preparations diabetes mellitus Mesangial Cells Animals Diabetic Nephropathies ONO-1301 Cells Cultured Chemokine CCL2 |
| Zdroj: | Acta medica Okayama. 69(1) |
| ISSN: | 0386-300X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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