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Aliskiren ameliorates renal inflammation and fibrosis induced by unilateral ureteral obstruction in mice

 Dae Eun Choi  ;  Jin Young Jeong  ;  Beom Jin Lim  ;  Yoon-Kyung Chang  ;  Ki-Ryang Na  ;  Young-Tai Shin  ;  Kang Wook Lee 
 JOURNAL OF UROLOGY, Vol.186(2) : 694-701, 2011 
Journal Title
Issue Date
Amides/therapeutic use* ; Animals ; Fibrosis/drug therapy ; Fibrosis/etiology ; Fumarates/therapeutic use* ; Kidney/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Nephritis/drug therapy* ; Nephritis/etiology ; Renin/antagonists & inhibitors* ; Ureteral Obstruction/complications
ureteral obstruction ; aliskiren ; renin-angiotensin system ; inflammation ; fibrosis
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.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Lim, Beom Jin(임범진) ORCID logo https://orcid.org/0000-0003-2856-0133
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