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Aliskiren Ameliorates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction in Mice

医学 肾病科 内科学 艾莉斯基伦 炎症 肾素-血管紧张素系统 纤维化 血压
作者
Dae Eun Choi,Jin Young Jeong,Beom Jin Lim,Yoon-Kyung Chang,Ki Ryang Na,Young-Tai Shin,Kang Wook Lee
出处
期刊:The Journal of Urology [Ovid Technologies (Wolters Kluwer)]
卷期号:186 (2): 694-701 被引量:48
标识
DOI:10.1016/j.juro.2011.03.122
摘要

No AccessJournal of UrologyInvestigative Urology1 Aug 2011Aliskiren Ameliorates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction in Miceis corrected byErratum Dae Eun Choi, Jin Young Jeong, Beom Jin Lim, Yoon-Kyung Chang, Ki-Ryang Na, Young-Tai Shin, and Kang Wook Lee Dae Eun ChoiDae Eun Choi Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea , Jin Young JeongJin Young Jeong Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea , Beom Jin LimBeom Jin Lim Daejeon St. Mary Hospital, Daejeon, South Korea , Yoon-Kyung ChangYoon-Kyung Chang Department of Pathology, Yonsei University Gangnam Severance Hospital, Seoul, South Korea , Ki-Ryang NaKi-Ryang Na Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea , Young-Tai ShinYoung-Tai Shin Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea , and Kang Wook LeeKang Wook Lee Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea View All Author Informationhttps://doi.org/10.1016/j.juro.2011.03.122AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Renin-angiotensin system activation is involved in inflammation and fibrosis in the kidney. Aliskiren, a direct renin inhibitor, decreases renin-angiotensin system activation, including plasma renin activity and angiotensin II, but increases the prorenin level, which may promote inflammation and fibrosis in renal tissue. Thus, we evaluated whether inhibiting the renin-angiotensin system by aliskiren would decrease renal inflammation and fibrosis in a mouse model of unilateral ureteral obstruction. Materials and Methods: Ten-week-old male C57BL/6 mice (Samtako, Kyoung Gi-Do, Korea) weighing 30 to 33 gm were divided into 4 groups, including vehicle or aliskiren treated sham operated and vehicle or aliskiren treated unilateral ureteral obstruction groups. We evaluated plasma renin activity, and plasma renin and renal mRNA expression levels of renin and (pro)renin receptor. To evaluate inflammation and fibrosis renal mRNA expression of monocyte chemotactic protein-1, osteopontin and transforming growth factor-β was measured. Hematoxylin and eosin, Masson's trichrome staining, and immunohistochemical staining for CD68, transforming growth factor-β and α-smooth muscle actin were performed. Results: Plasma renin activity was significantly lower in the aliskiren treated obstruction group than in the vehicle treated obstruction group. Aliskiren treatment increased renal mRNA expression of renin. The number of CD68 positive cells, and renal monocyte chemotactic protein-1 and osteopontin mRNA levels were significantly higher in mice with unilateral ureteral obstruction than in sham operated mice. Aliskiren decreased the increased levels of these inflammation markers. Aliskiren also decreased renal transforming growth factor-β mRNA expression, transforming growth factor-β and α-smooth muscle actin immunostaining, and Masson's trichrome stained areas of unilateral ureteral obstruction kidneys. Conclusions: Aliskiren has anti-inflammatory and antifibrotic effects in an experimental unilateral ureteral obstruction mouse model. References 1 : The progression of renal disease. N Engl J Med1988; 318: 1657. Google Scholar 2 : Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol2002; 283: F861. Google Scholar 3 : Obstructive nephropathy: insights from genetically engineered animals. Kidney Int2005; 68: 925. Google Scholar 4 Burns WC, Velkoska E, Dean R et al: Angiotensin II mediates epithelial-to-mesenchymal transformation in tubular cells by ANG 1-7/MAS-1-dependent pathways. Am J Physiol Renal Physiol; 299: F585. Google Scholar 5 : Effects of suppressing intrarenal angiotensinogen on renal transforming growth factor-beta1 expression in acute ureteral obstruction. Kidney Int2005; 67: 897. Google Scholar 6 : ACE inhibitors improve diabetic nephropathy through suppression of renal MCP-1. Diabetes Care2003; 26: 2421. 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Google Scholar © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited BySakuraya K, Endo A, Someya T, Hirano D, Murano Y, Fujinaga S, Ohtomo Y and Shimizu T (2018) The Synergistic Effect of Mizoribine and a Direct Renin Inhibitor, Aliskiren, on Unilateral Ureteral Obstruction Induced Renal Fibrosis in RatsJournal of Urology, VOL. 191, NO. 4, (1139-1146), Online publication date: 1-Apr-2014.Related articlesJournal of Urology22 Aug 2011Erratum Volume 186Issue 2August 2011Page: 694-701 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Keywordsfibrosisureteral obstructionaliskirenrenin-angiotensin systeminflammationAcknowledgmentsAliskiren powder was supplied by Novartis, East Hanover, New Jersey.MetricsAuthor Information Dae Eun Choi Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea More articles by this author Jin Young Jeong Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea More articles by this author Beom Jin Lim Daejeon St. Mary Hospital, Daejeon, South Korea More articles by this author Yoon-Kyung Chang Department of Pathology, Yonsei University Gangnam Severance Hospital, Seoul, South Korea More articles by this author Ki-Ryang Na Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea More articles by this author Young-Tai Shin Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea More articles by this author Kang Wook Lee Departments of Nephrology, Chungnam National University Hospital, Daejeon, South Korea More articles by this author Expand All Advertisement PDF DownloadLoading ...
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