2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ma, J. Articles by Ichikawa, I. Search for Related Content PubMed PubMed Citation Articles by Ma, J. Articles by Ichikawa, I.

Local Actions of Endogenous Angiotensin II in Injured Glomeruli

Ji Ma^*,,, Taiji Matsusaka^*,, Haichun Yang, Hiroshi Kawachi, Fujio Shimizu, Yoshitaka Isaka^¶, Enyu Imai^¶, Valentina Kon and Iekuni Ichikawa^*,

*Department of Pediatrics, Tokai University School of Medicine, Isehara, Japan; Division of Nephrology, Hua Shan Hospital, Fudan University, Shanghai, China; Division of Pediatric Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; ¶Division of Nephrology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.

Correspondence to Dr. Ji Ma, Pediatric Nephrology, Vanderbilt University Medical Center, 1161 21^st. Ave. S. MCN C4204, Nashville, TN 37232. Phone: 615-322-7416; Fax: 615-322-7929; E-mail: ji.ma{at}vanderbilt.edu

ABSTRACT. A previous study showed that exogenous angiotensin II (AngII) induces proliferation of glomerular cells through systemic actions of AngII. In the present study, the authors examined the mode of actions of endogenous AngII in injured kidneys that were made deficient in AT1 by using in vivo transfection of antisense oligodeoxynucleotide (AS-ODN). Thy-1 nephritis was induced in rats by injection of mAb 1-22-3. Four days later, glomerular transfection was performed by unilateral whole-kidney electroporation after AT1 AS-ODN delivery through the left renal artery (n = 7). The expression of renal AT1 was assessed by autoradiography. The effect of the AS-ODN transfection was assessed 3 d later and compared with transfection with control ODN (n = 6), systemically administered pharmacologic AT1 antagonist losartan (n = 5) as well as untreated Thy-1 animals (n = 5). Fluorescence-labeled AS-ODN was found transfected in almost all glomeruli and localized primarily to the mesangium. Compared with the contralateral untransfected kidney in both normal and Thy-1 rats, AS-ODN suppressed cortical AT1 expression by some 70%. The AS-ODN transfected kidneys of Thy-1 rats had significantly lower glomerular mesangial cell proliferation (7.38 ± 0.68 cells/glomerulus) and extracellular matrix accumulation (0.262 ± 0.009) than kidneys transfected with control ODN (10.94 ± 0.51 cells/glomerulus and 0.342 ± 0.031), contralateral untransfected kidneys (9.56 ± 1.01 cells/glomerulus and 0.371 ± 0.011), or kidneys that were exposed to Thy-1 alone (10.45 ± 1.06 cells/glomerulus and 0.359 ± 0.013). There were no significant differences in systolic BP among groups. In glomeruli, immunohistochemistry detected no difference in AT2 receptor expression, number of ED1-positive macrophages or number of apoptotic cells among groups. Thus, in renal injury induced by Thy-1 nephritis, selective suppression of mesangial AT1 expression by AS-ODN significantly reduced mesangial cell proliferation and matrix. These data provide in vivo evidence that injured glomeruli are sensitive to local tissue actions of AngII, which promote proliferation and matrix accumulation within the glomerulus.

This article has been cited by other articles:

				P Fu, P-J Shen, C-X Zhao, D J Scott, C S Samuel, J D Wade, G W Tregear, R A D Bathgate, and A L Gundlach Leucine-rich repeat-containing G-protein-coupled receptor 8 in mature glomeruli of developing and adult rat kidney and inhibition by insulin-like peptide-3 of glomerular cell proliferation. J. Endocrinol., May 1, 2006; 189(2): 397 - 408. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673