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 Freeburg, P. B. Articles by Abrahamson, D. R. Search for Related Content PubMed PubMed Citation Articles by Freeburg, P. B. Articles by Abrahamson, D. R.

Podocyte Expression of Hypoxia-Inducible Factor (HIF)–1 and HIF–2 during Glomerular Development

Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas.

Correspondence to Dale R. Abrahamson, Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160-7400. Phone: 913-588-7000; Fax: 913-588-2710;

ABSTRACT. The heterodimeric transcription factors, hypoxia-inducible factor (HIF)–1 and HIF-2, are essential for the maintenance of cellular oxygen homeostasis. In response to hypoxia, stabilized HIF-1 and HIF-2 proteins bind HIF-1 and initiate expression of genes that alleviate hypoxic stress, including those promoting neovascularization. Both HIF-1 and HIF-2 stimulate transcription of vascular endothelial growth factor (VEGF), a crucial regulator of vascular development. Because VEGF is highly expressed by metanephric podocytes and collecting ducts, developing mouse kidney was examined for the presence and distribution of HIF-1, HIF-2, and HIF-1. The expression of HIF-1 and HIF-2 mRNAs in newborn mouse kidney was confirmed by RT-PCR and Northern blot analysis. By in situ hybridization, HIF-1 and HIF-2 mRNAs were highly expressed in the nephrogenic zone of newborn kidney cortex and in the medulla. Particularly intense hybridization was found in podocytes of developing glomeruli and in medullary collecting ducts. Both HIF-1 and HIF-2 heterodimers were identified in newborn kidney lysates by immunoprecipitation with HIF-1, HIF-2, and HIF-1 antibodies and Western blots. Immunofluorescence analysis of the hypoxia marker, pimonidazole, showed that collecting ducts and many developing tubules undergo severe hypoxia in developing kidney. Immunohistochemistry of newborn kidney demonstrated widespread expression of HIF-1 protein in nuclei of glomeruli and all tubular segments, whereas HIF-2 protein expression was more restricted and localized chiefly to podocytes of developing glomeruli and developing tubules. HIF-1 and HIF-2 protein and VEGF mRNA were all strongly induced in embryonic kidneys maintained in hypoxic organ cultures. Collectively, these data suggest that HIF stabilization, by hypoxia and/or by other means, may be critical for VEGF production and kidney vascular development. E-mail: dabrahamson@kumc.edu

This article has been cited by other articles:

				K. Brukamp, B. Jim, M. J. Moeller, and V. H. Haase Hypoxia and podocyte-specific Vhlh deletion confer risk of glomerular disease Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1397 - F1407. [Abstract] [Full Text] [PDF]

				H. Makino, Y. Miyamoto, K. Sawai, K. Mori, M. Mukoyama, K. Nakao, Y. Yoshimasa, and S.-i. Suga Altered Gene Expression Related to Glomerulogenesis and Podocyte Structure in Early Diabetic Nephropathy of db/db Mice and Its Restoration by Pioglitazone. Diabetes, October 1, 2006; 55(10): 2747 - 2756. [Abstract] [Full Text] [PDF]

				V. H. Haase Hypoxia-inducible factors in the kidney Am J Physiol Renal Physiol, August 1, 2006; 291(2): F271 - F281. [Abstract] [Full Text] [PDF]

				C. Petry, A. Huwiler, W. Eberhardt, M. Kaszkin, and J. Pfeilschifter Hypoxia Increases Group IIA Phospholipase A2 Expression under Inflammatory Conditions in Rat Renal Mesangial Cells J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2897 - 2905. [Abstract] [Full Text] [PDF]

				G. Wolf, S. Chen, and F. N. Ziyadeh From the Periphery of the Glomerular Capillary Wall Toward the Center of Disease: Podocyte Injury Comes of Age in Diabetic Nephropathy Diabetes, June 1, 2005; 54(6): 1626 - 1634. [Abstract] [Full Text] [PDF]

				P. B. Freeburg and D. R. Abrahamson Divergent Expression Patterns for Hypoxia-Inducible Factor-1{beta} and Aryl Hydrocarbon Receptor Nuclear Transporter-2 in Developing Kidney J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2569 - 2578. [Abstract] [Full Text] [PDF]

				K. Manotham, T. Tanaka, M. Matsumoto, T. Ohse, T. Miyata, R. Inagi, K. Kurokawa, T. Fujita, and M. Nangaku Evidence of Tubular Hypoxia in the Early Phase in the Remnant Kidney Model J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1277 - 1288. [Abstract] [Full Text] [PDF]

				H.-T. Yuan, X.-Z. Li, J. E. Pitera, D. A. Long, and A. S. Woolf Peritubular Capillary Loss after Mouse Acute Nephrotoxicity Correlates with Down-Regulation of Vascular Endothelial Growth Factor-A and Hypoxia-Inducible Factor-1{alpha} Am. J. Pathol., December 1, 2003; 163(6): 2289 - 2301. [Abstract] [Full Text]

				P. B. Freeburg and D. R. Abrahamson Hypoxia-Inducible Factors and Kidney Vascular Development J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2723 - 2730. [Abstract] [Full Text] [PDF]

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