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Cellular Origins of Type IV Collagen Networks in Developing Glomeruli

Dale R. Abrahamson^*, Billy G. Hudson, Larysa Stroganova^*, Dorin-Bogdan Borza and Patricia L. St. John^*

^* Department of Anatomy and Cell Biology, and The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, and Department of Medicine, and Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee

Correspondence: Dr. Dale R. Abrahamson, Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, MS 3038, Kansas City, KS 66160. Phone: 913-588-7000; Fax: 913-588-2710; E-mail: dabrahamson{at}kumc.edu

Received for publication October 17, 2008. Accepted for publication February 6, 2009.

Laminin and type IV collagen composition of the glomerular basement membrane changes during glomerular development and maturation. Although it is known that both glomerular endothelial cells and podocytes produce different laminin isoforms at the appropriate stages of development, the cellular origins for the different type IV collagen heterotrimers that appear during development are unknown. Here, immunoelectron microscopy demonstrated that endothelial cells, mesangial cells, and podocytes of immature glomeruli synthesize collagen 121(IV). However, intracellular labeling revealed that podocytes, but not endothelial or mesangial cells, contain collagen 345(IV). To evaluate the origins of collagen IV further, we transplanted embryonic kidneys from Col4a3-null mutants (Alport mice) into kidneys of newborn, wildtype mice. Hybrid glomeruli within grafts containing numerous host-derived, wildtype endothelial cells never expressed collagen 345(IV). Finally, confocal microscopy of glomeruli from infant Alport mice that had been dually labeled with anti-collagen 5(IV) and the podocyte marker anti-GLEPP1 showed immunolabeling exclusively within podocytes. Together, these results indicate that collagen 345(IV) originates solely from podocytes; therefore, glomerular Alport disease is a genetic defect that manifests specifically within this cell type.

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J. Am. Soc. Nephrol. 2009 20: A13. [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673