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 AZUMA, H. Articles by NAKAMURA, T. Search for Related Content PubMed PubMed Citation Articles by AZUMA, H. Articles by NAKAMURA, T.

Hepatocyte Growth Factor Prevents the Development of Chronic Allograft Nephropathy in Rats

HARUHITO AZUMA^*, SHIRO TAKAHARA, KUNIO MATSUMOTO, NAOTSUGU ICHIMARU, JING DING WANG, TOSHIKI MORIYAMA^||, ANA-MARIA WAAGA^¶, MASAYA KITAMURA, YOSHINORI OTSUKI, AKIHIKO OKUYAMA, YOJI KATSUOKA^*, ANIL CHANDRAKER^¶, MOHAMED H. SAYEGH^¶ and TOSHIKAZU NAKAMURA

^* Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Anatomy and Biology, Osaka Medical College, Osaka, Japan
Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan
Division of Biochemistry, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka, Japan
^|| Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan
^¶ Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Correspondence to Dr. Shiro Takahara, Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: +81-6-6879-3531; Fax: +81-6-6879-3539; E-mail: takahara{at}uro.med.osaka-u.ac.jp

Abstract. Long-term renal isografts in humans and laboratory animals exhibit features similar to those of chronic allograft nephropathy (CAN), indicating that antigen-independent factors, such as acute renal ischemia, are likely to be involved in the development of CAN. Hepatocyte growth factor (HGF) has been demonstrated to play a renotropic role in renal regeneration and protection from acute ischemic injury. This study was thus conducted to investigate the effect of HGF on the development of CAN, using an established rat model. HGF was administered daily (100 µg/d, intravenously) for 4 wk after engraftment. Control animals received saline solution. Allografts from control animals exhibited early evidence of severe structural collapse and necrotic cell death in the proximal tubules and outer medulla, with mononuclear cell infiltration, within 1 wk after engraftment. This was followed by sequential upregulation of adhesion molecules and cytokines, accompanied by dense macrophage infiltration. Fibrogenic events, as indicated by marked increases in transforming growth factor-ß1 expression and the accumulation of smooth muscle -actin, occurred during the same period. Control animals ultimately developed features typical of CAN, with functional deterioration and severe histologic changes; a survival rate of 50.6% by 32 wk was observed. In contrast, remarkably little early injury and no late fibrogenic events were observed for the HGF-treated group. All treated animals survived, with well preserved graft function, during the 32-wk follow-up period. These results indicate that renal protection and recovery from early allograft injury with HGF treatment greatly contribute to a reduction of susceptibility to the subsequent development of CAN in a rat model. The potential application of HGF in the prevention of CAN warrants further attention.

This article has been cited by other articles:

				M. Giannopoulou, C. Dai, X. Tan, X. Wen, G. K. Michalopoulos, and Y. Liu Hepatocyte Growth Factor Exerts Its Anti-Inflammatory Action by Disrupting Nuclear Factor-{kappa}B Signaling Am. J. Pathol., July 1, 2008; 173(1): 30 - 41. [Abstract] [Full Text] [PDF]

				A. M. Jevnikar and R. B. Mannon Late Kidney Allograft Loss: What We Know about It, and What We Can Do about It Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(Supplement_2): S56 - S67. [Abstract] [Full Text] [PDF]

				R. Tan, X. Zhang, J. Yang, Y. Li, and Y. Liu Molecular Basis for the Cell Type Specific Induction of SnoN Expression by Hepatocyte Growth Factor J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2340 - 2349. [Abstract] [Full Text] [PDF]

				A. Zhang, M.-H. Wang, Z. Dong, and T. Yang Prostaglandin E2 is a potent inhibitor of epithelial-to-mesenchymal transition: interaction with hepatocyte growth factor Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1323 - F1331. [Abstract] [Full Text] [PDF]

				M. L. Marco The Fischer-Lewis model of chronic allograft rejection--a summary Nephrol. Dial. Transplant., November 1, 2006; 21(11): 3082 - 3086. [Abstract] [Full Text] [PDF]

				N. Beckmann, C. Cannet, S. Zurbruegg, R. Haberthur, J. Li, C. Pally, and C. Bruns Macrophage Infiltration Detected at MR Imaging in Rat Kidney Allografts: Early Marker of Chronic Rejection? Radiology, September 1, 2006; 240(3): 717 - 724. [Abstract] [Full Text] [PDF]

				S. Mizuno and T. Nakamura Prevention of Neutrophil Extravasation by Hepatocyte Growth Factor Leads to Attenuations of Tubular Apoptosis and Renal Dysfunction in Mouse Ischemic Kidneys Am. J. Pathol., June 1, 2005; 166(6): 1895 - 1905. [Abstract] [Full Text] [PDF]

				J. Yang, C. Dai, and Y. Liu A Novel Mechanism by which Hepatocyte Growth Factor Blocks Tubular Epithelial to Mesenchymal Transition J. Am. Soc. Nephrol., January 1, 2005; 16(1): 68 - 78. [Abstract] [Full Text] [PDF]

				C. Dai, J. Yang, S. Bastacky, J. Xia, Y. Li, and Y. Liu Intravenous Administration of Hepatocyte Growth Factor Gene Ameliorates Diabetic Nephropathy in Mice J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2637 - 2647. [Abstract] [Full Text] [PDF]

				K. Yamaura, K.-i. Ito, K. Tsukioka, Y. Wada, A. Makiuchi, M. Sakaguchi, T. Akashima, M. Fujimori, Y. Sawa, R. Morishita, et al. Suppression of Acute and Chronic Rejection by Hepatocyte Growth Factor in a Murine Model of Cardiac Transplantation: Induction of Tolerance and Prevention of Cardiac Allograft Vasculopathy Circulation, September 21, 2004; 110(12): 1650 - 1657. [Abstract] [Full Text] [PDF]

				Y. Liu Hepatocyte growth factor in kidney fibrosis: therapeutic potential and mechanisms of action Am J Physiol Renal Physiol, July 1, 2004; 287(1): F7 - F16. [Abstract] [Full Text] [PDF]

				J. M. Cruzado, N. Lloberas, J. Torras, M. Riera, C. Fillat, I. Herrero-Fresneda, J. M. Aran, G. Alperovich, A. Vidal, and J. M. Grinyo Regression of Advanced Diabetic Nephropathy by Hepatocyte Growth Factor Gene Therapy in Rats Diabetes, April 1, 2004; 53(4): 1119 - 1127. [Abstract] [Full Text] [PDF]

				Y. Liu Epithelial to Mesenchymal Transition in Renal Fibrogenesis: Pathologic Significance, Molecular Mechanism, and Therapeutic Intervention J. Am. Soc. Nephrol., January 1, 2004; 15(1): 1 - 12. [Abstract] [Full Text] [PDF]

				S. Mizuno and T. Nakamura Suppressions of chronic glomerular injuries and TGF-{beta}1 production by HGF in attenuation of murine diabetic nephropathy Am J Physiol Renal Physiol, January 1, 2004; 286(1): F134 - F143. [Abstract] [Full Text] [PDF]

				R. Poulsom, M. R. Alison, T. Cook, R. Jeffery, E. Ryan, S. J. Forbes, T. Hunt, S. Wyles, and N. A. Wright Bone Marrow Stem Cells Contribute to Healing of the Kidney J. Am. Soc. Nephrol., June 1, 2003; 14(90001): S48 - 54. [Abstract] [Full Text] [PDF]

				J. Yang and Y. Liu Delayed administration of hepatocyte growth factor reduces renal fibrosis in obstructive nephropathy Am J Physiol Renal Physiol, February 1, 2003; 284(2): F349 - F357. [Abstract] [Full Text] [PDF]

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