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) All Versions of this Article: ASN.2004121117v1 16/8/2306    most recent 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 Chan, L. Y.Y. Articles by Lai, K. N. Search for Related Content PubMed PubMed Citation Articles by Chan, L. Y.Y. Articles by Lai, K. N. Related Collections Related Article

Tubular Expression of Angiotensin II Receptors and Their Regulation in IgA Nephropathy

Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong

Address correspondence to: Prof. Kar Neng Lai, Department of Medicine, Room 411, Professorial Block, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong. Phone: 852-2855-4251; Fax: 852-2816-2863; E-mail: knlai{at}hkucc.hku.hk

Received for publication December 21, 2004. Accepted for publication April 30, 2005.

Enhanced renal expression for the renin-angiotensin system (RAS) is detected in IgA nephropathy (IgAN). Previous data showed an altered glomerular expression of angiotensin II type 1 receptor (AT1R), suggesting a regulatory response to high intrarenal angiotensin II (Ang II) concentration in IgAN. In this study, the expression and regulation of Ang II receptors were examined in human proximal tubular epithelial cells (PTEC) in IgAN. Tubular expression of AT1R and Ang II type 2 receptor (AT2R) was increased in IgAN. In vitro culture experiment showed that the upregulation of Ang II receptors was not due to the direct effect of IgA but the indirect effect after IgA deposition on human mesangial cell. When PTEC were cultured with conditioned culture medium from human mesangial cells activated with IgA, Ang II production was upregulated, leading to inflammation and apoptosis via the AT1R and AT2R, respectively. Sequential expression of Ang II receptors determined the injury of PTEC induced by mediators in the conditioned medium. The initial interaction between Ang II and AT1R activated both protein kinase C and mitogen-activated protein kinase pathways, leading to inflammatory responses. This early AT1R-dependent event was followed by upregulation of AT2R expression and continued Ang II release. The interaction between Ang II and AT2R subsequently led to expression of cleaved poly[ADP-ribose] polymerase through downregulation of the mitogen-activated protein kinase pathway. The data suggest that appropriate control of Ang II receptor activities in PTEC may ameliorate tubulointerstitial injury in IgAN.

Related Article

This Month’s Highlights
J. Am. Soc. Nephrol. 2005 16: 2243-2244. [Full Text] [PDF]

This article has been cited by other articles:

				S. R. Holdsworth and S. A. Summers Role of Mast Cells in Progressive Renal Diseases J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2254 - 2261. [Abstract] [Full Text] [PDF]

				K. N. Lai, J. C. K. Leung, L. Y. Y. Chan, M. A. Saleem, P. W. Mathieson, K. Y. Tam, J. Xiao, F. M. Lai, and S. C. W. Tang Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy Nephrol. Dial. Transplant., August 6, 2008; (2008) gfn441v1. [Abstract] [Full Text] [PDF]

				K. N. Lai, J. C. K. Leung, L. Y. Y. Chan, M. A. Saleem, P. W. Mathieson, F. M. Lai, and S. C. W. Tang Activation of podocytes by mesangial-derived TNF-{alpha}: glomerulo-podocytic communication in IgA nephropathy Am J Physiol Renal Physiol, April 1, 2008; 294(4): F945 - F955. [Abstract] [Full Text] [PDF]

				H. Kobori, M. Nangaku, L. G. Navar, and A. Nishiyama The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease Pharmacol. Rev., September 1, 2007; 59(3): 251 - 287. [Abstract] [Full Text] [PDF]

				H. Haller, J.-K. Park, C. Lindschau, M. Meyer, and J. Menne Intrarenal renin-angiotensin system -- important player of the local milieu Journal of Renin-Angiotensin-Aldosterone System, June 1, 2006; 7(2): 122 - 125. [PDF]

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