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.2006080820v1 18/7/2054    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 Takahashi, H. Articles by Itoh, H. Search for Related Content PubMed PubMed Citation Articles by Takahashi, H. Articles by Itoh, H.

Regression of Nephropathy Developed in Diabetes by (Pro)renin Receptor Blockade

Hidena Takahashi^*, Atsuhiro Ichihara^*, Yuki Kaneshiro^*, Kenta Inomata^*, Mariyo Sakoda^*, Tomoko Takemitsu^*, Akira Nishiyama and Hiroshi Itoh^*

^* Internal Medicine, Keio University School of Medicine, Tokyo, and Pharmacology, Kagawa University School of Medicine, Kagawa, Japan

Correspondence: Dr. Atsuhiro Ichihara, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. Phone: +81-3-5363-3796; Fax: +81-3-3359-2745; E-mail: atzichi{at}sc.itc.keio.ac.jp

Received for publication August 3, 2006. Accepted for publication April 10, 2007.

Activation of prorenin by (pro)renin receptor stimulates the tissue renin-angiotensin system and plays a significant role in the development of nephropathy in diabetic animals. This study examined whether (pro)renin receptor blockade inhibits the progression of nephropathy that has already developed in diabetic rats. Seventeen-week-old heminephrectomized streptozotocin-induced diabetic rats with an increased urinary protein excretion and a significant glomerulosclerosis had been treated for 12 wk with the (pro)renin receptor blocker (PRRB), angiotensin-converting enzyme inhibitor (ACEi), or vehicle peptide by using subcutaneously implanted osmotic minipumps. At the end of observation, in diabetic rats that were treated with vehicle, urinary protein excretion was progressively increased and a significant progression of glomerulosclerosis was observed. In diabetic rats that were treated with PRRB, however, no further increase in urinary protein excretion or glomerulosclerosis was observed, but 12-wk treatment with ACEi only attenuated further increases in urinary protein excretion and glomerulosclerosis. The enhanced expression of activated prorenin was observed in the kidneys of diabetic rats that were treated with vehicle, whereas it was markedly suppressed in the kidneys of diabetic rats that were treated with PRRB but not ACEi. These results suggest that (pro)renin receptor blockade does not only inhibit the progression of nephropathy but also reverses the glomerulosclerosis that has already developed in diabetic rats.

This article has been cited by other articles:

				S. Satofuka, A. Ichihara, N. Nagai, K. Noda, Y. Ozawa, A. Fukamizu, K. Tsubota, H. Itoh, Y. Oike, and S. Ishida (Pro)renin Receptor Promotes Choroidal Neovascularization by Activating Its Signal Transduction and Tissue Renin-Angiotensin System Am. J. Pathol., December 1, 2008; 173(6): 1911 - 1918. [Abstract] [Full Text] [PDF]

				J. Peti-Peterdi, J. J. Kang, and I. Toma Activation of the renal renin-angiotensin system in diabetes--new concepts Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3047 - 3049. [Full Text] [PDF]

				A. J. Danser and G. Nguyen Spotlight on Renin: The Renin Academy Summit: advancing the understanding of renin science Journal of Renin-Angiotensin-Aldosterone System, June 1, 2008; 9(2): 119 - 123. [PDF]

				G. Nguyen and A. H. J. Danser Prorenin and (pro)renin receptor: a review of available data from in vitro studies and experimental models in rodents Exp Physiol, May 1, 2008; 93(5): 557 - 563. [Abstract] [Full Text] [PDF]

				D. J. Campbell Critical Review of Prorenin and (Pro)renin Receptor Research Hypertension, May 1, 2008; 51(5): 1259 - 1264. [Full Text] [PDF]

				R. V. Durvasula and S. J. Shankland Activation of a local renin angiotensin system in podocytes by glucose Am J Physiol Renal Physiol, April 1, 2008; 294(4): F830 - F839. [Abstract] [Full Text] [PDF]

				A. Ichihara, A. Nishiyama, T. Nakagawa, F. Suzuki, T. Inagami, and H. Itoh Significant roles of prorenin and (pro)renin receptor in development and progression of diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System, March 1, 2008; 9(1_suppl): S5 - S6. [PDF]

				D. N. Muller, B. Klanke, S. Feldt, N. Cordasic, A. Hartner, R. E. Schmieder, F. C. Luft, and K. F. Hilgers (Pro)Renin Receptor Peptide Inhibitor "Handle-Region" Peptide Does Not Affect Hypertensive Nephrosclerosis in Goldblatt Rats Hypertension, March 1, 2008; 51(3): 676 - 681. [Abstract] [Full Text] [PDF]

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