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.2004050392v1 16/2/363    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 Lassila, M. Articles by Cooper, M. E. Search for Related Content PubMed PubMed Citation Articles by Lassila, M. Articles by Cooper, M. E.

Imatinib Attenuates Diabetic Nephropathy in Apolipoprotein E-Knockout Mice

Markus Lassila^*, Karin Jandeleit-Dahm^*, Kwee K. Seah^*, Craig M. Smith^*, Anna C. Calkin^*,, Terri J. Allen^* and Mark E. Cooper^*

^* Danielle Alberti Memorial Centre for Diabetes Complications, Wynn Domain, Baker Heart Research Institute, Melbourne, Victoria, Australia; and Department of Medicine, Central and Eastern Clinical School, Monash University, Alfred Hospital, Melbourne, Victoria, Australia

Address correspondence to: Prof. Mark E. Cooper, Baker Heart Research Institute, P.O. Box 6492, Commercial Road, Melbourne 8008, VIC 3004, Australia. Phone: +613-8532-1362; Fax: +613-8532-1480; E-mail: mark.cooper{at}baker.edu.au

In the diabetic kidney, clinical as well as experimental observations have shown an upregulation of growth factors such as PDGF. These studies, however, were not designed to address whether upregulation of PDGF is merely a manifestation of diabetic renal injury or whether PDGF plays an active role in the pathophysiology of diabetic nephropathy. The objectives of this study were first to assess whether PDGF-dependent pathways are involved in the development of diabetic nephropathy and second to determine the effects of PDGF receptor antagonism on this disorder and associated molecular and cellular processes. This study used the diabetic apolipoprotein E-knockout (apoE-KO) mouse, a recently described model of accelerated diabetic nephropathy. Diabetes was induced by injection of streptozotocin in 6-wk-old apoE-KO mice. Diabetic animals received treatment with a tyrosine kinase inhibitor that inhibits PDGF action, imatinib (STI-571, 10 mg/kg per d orally) or no treatment for 20 wk. Nondiabetic apoE-KO mice served as controls. This model of accelerated renal disease with albuminuria as well as glomerular and tubulointerstitial injury was associated with increased renal expression of PDGF-B, proliferating cells, and -smooth muscle actin-positive cells. Furthermore, there was increased accumulation of type I and type IV collagen as well as macrophage infiltration. Imatinib treatment ameliorated both renal functional and structural parameters of diabetes as well as overexpression of a number of growth factors, collagens, proliferating cells, -smooth muscle actin-positive cells, and macrophage infiltration within the kidney. Tyrosine kinase inhibition with imatinib seems to retard the development of experimental diabetic nephropathy.

This article has been cited by other articles:

				J. Floege, F. Eitner, and C. E. Alpers A New Look at Platelet-Derived Growth Factor in Renal Disease J. Am. Soc. Nephrol., January 1, 2008; 19(1): 12 - 23. [Abstract] [Full Text] [PDF]

				P. Boor, K. Sebekova, T. Ostendorf, and J. Floege Treatment targets in renal fibrosis Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3391 - 3407. [Full Text] [PDF]

				T. Gonzalo, L. Beljaars, M. van de Bovenkamp, K. Temming, A.-M. van Loenen, C. Reker-Smit, D. K. F. Meijer, M. Lacombe, F. Opdam, G. Keri, et al. Local Inhibition of Liver Fibrosis by Specific Delivery of a Platelet-Derived Growth Factor Kinase Inhibitor to Hepatic Stellate Cells J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 856 - 865. [Abstract] [Full Text] [PDF]

				P. Dentelli, A. Rosso, A. Balsamo, S. Colmenares Benedetto, A. Zeoli, M. Pegoraro, G. Camussi, L. Pegoraro, and M. F. Brizzi C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium Blood, May 15, 2007; 109(10): 4264 - 4271. [Abstract] [Full Text] [PDF]

				P. Boor, A. Konieczny, L. Villa, U. Kunter, C. R.C. van Roeyen, W. J. LaRochelle, G. Smithson, S. Arrol, T. Ostendorf, and J. Floege PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis Nephrol. Dial. Transplant., May 1, 2007; 22(5): 1323 - 1331. [Abstract] [Full Text] [PDF]

				M. W.M. Schellings, M. Baumann, R. E.W. van Leeuwen, R. F.J.J. Duisters, S. H.P. Janssen, B. Schroen, C. J. Peutz-Kootstra, S. Heymans, and Y. M. Pinto Imatinib Attenuates End-Organ Damage in Hypertensive Homozygous TGR(mRen2)27 Rats Hypertension, March 1, 2006; 47(3): 467 - 474. [Abstract] [Full Text] [PDF]

				H. Suzuki and S. Eguchi Growth Factor Receptor Transactivation in Mediating End Organ Damage by Angiotensin II Hypertension, March 1, 2006; 47(3): 339 - 340. [Full Text] [PDF]

				K. A. JANDELEIT-DAHM, M. LASSILA, and T. J. ALLEN Advanced Glycation End Products in Diabetes-Associated Atherosclerosis and Renal Disease: Interventional Studies Ann. N.Y. Acad. Sci., June 1, 2005; 1043(1): 759 - 766. [Abstract] [Full Text] [PDF]

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