Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice

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	Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice
	Wu, Jin ; Guan, Tian-jun ; Zheng, Shirong ; Grosjean, Fabrizio ; Liu, Weicheng ; Xiong, Huabao ; Gordon, Ronald ; Vlassara, Helen ; Striker, Gary E. ; Zheng, Feng ; Guan TJ(关天俊) ; Zheng F(郑丰)
刊名	http://dx.doi.org/10.1038/labinvest.2011.93
	2011-10
关键词	DIRECT RENIN INHIBITORS RENAL INJURY SIGNALING PATHWAYS MACROPHAGE RECRUITMENT KIDNEY-DISEASE DB/DB MICE EXPRESSION ALBUMINURIA RECEPTOR RATS
英文摘要	NIH [5R01AG027628-03]; Genzyme Grant; JDRF [17-2008-1041]; Inflammation has a key role in diabetic nephropathy (DN) progression. Pentosan polysulfate (PPS) has been shown to decreases interstitial inflammation and glomerulosclerosis in 5/6 nephrectomized rats. Since PPS has an excellent long-term safety profile in interstitial cystitis treatment, and we recently found that old diabetic C57B6 mice develop DN characterized by extensive tubulointerstitial inflammatory lesions that mimics human DN, we examined the effect of PPS on old diabetic mice. We also examined the anti-inflammatory properties of PPS in renal cells in vitro. Diabetes was induced with streptozotocin in 18 months female (early aging) C57B6 mice. Mice were then randomized to receive oral PPS (25 mg/kg/day) or water for 4 months. The effect of PPS on NF-kappa B activation and on TNF alpha, high glucose or advanced glycation end products (AGEs) stimulated proinflammatory gene expression in renal cells was examined. We found that PPS treatment preserved renal function, significantly reduced albuminuria, and markedly decreased the severity of renal lesions, including tubulointerstitial inflammation. PPS also reduced upregulation of TNF alpha and proinflammatory genes in aging diabetic kidneys. Furthermore, PPS suppressed NF-kappa B, decreased the proinflammatory actions of TNF alpha, and decreased high glucose and AGEs stimulated MCP-1 production in vitro. Finally, PPS decreased TNF alpha-induced increase in albumin permeability in podocyte monolayers. In conclusion, PPS treatment largely prevents the development/progression of nephropathy in aging diabetic mice. As this may be mediated by suppression of TNF alpha, high glucose, and AGE-stimulated NF-kappa B activation and inflammation in vitro, the in vivo blockade of DN may be due to the anti-inflammatory properties of PPS. Laboratory Investigation (2011) 91, 1459-1471; doi:10.1038/labinvest.2011.93; published online 1 August 2011
语种	英语
出版者	LAB INVEST
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93228]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Wu, Jin,Guan, Tian-jun,Zheng, Shirong,et al. Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice[J]. http://dx.doi.org/10.1038/labinvest.2011.93,2011.
APA	Wu, Jin.,Guan, Tian-jun.,Zheng, Shirong.,Grosjean, Fabrizio.,Liu, Weicheng.,...&郑丰.(2011).Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice.http://dx.doi.org/10.1038/labinvest.2011.93.
MLA	Wu, Jin,et al."Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice".http://dx.doi.org/10.1038/labinvest.2011.93 (2011).