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Renal Structural and Functional Repair in a Mouse Model of Reversal of Ureteral Obstruction

Anita L. Cochrane^*, Michelle M. Kett, Chrishan S. Samuel, Naomi V. Campanale^*, Warwick P. Anderson, David A. Hume, Melissa H. Little, John F. Bertram^|| and Sharon D. Ricardo^*,||

^* Monash Immunology and Stem Cell Laboratories, Departments of Physiology and ^|| Anatomy and Cell Biology, Monash University, Melbourne, Victoria, Australia; Howard Florey Research Institute, University of Melbourne, Melbourne, Victoria, Australia; and Institute for Molecular Bioscience, University of Queensland, Victoria, Australia

Address correspondence to: Dr. Sharon D. Ricardo, Monash Immunology and Stem Cell Laboratories, STRIP1, Level 3, Monash University, Clayton, Victoria 3800, Australia. Phone: +61-03-9905-9096; Fax: +61-03-9905-2766; E-mail: sharon.ricardo{at}med.monash.edu.au

Received for publication September 16, 2004. Accepted for publication August 22, 2005.

The end point of immune and nonimmune renal injury typically involves glomerular and tubulointerstitial fibrosis. Although numerous studies have focused on the events that lead to renal fibrosis, less is known about the mechanisms that promote cellular repair and tissue remodeling. Described is a model of renal injury and repair after the reversal of unilateral ureteral obstruction (UUO) in male C57bl/6J mice. Male mice (20 to 25 g) underwent 10 d of UUO with or without 1, 2, 4, or 6 wk of reversal of UUO (R-UUO). UUO resulted in cortical tubular cell atrophy and tubular dilation in conjunction with an almost complete ablation of the outer medulla. This was associated with interstitial macrophage infiltration; increased hydroxyproline content; and upregulated type I, III, IV, and V collagen expression. The volume density of kidney occupied by renal tubules that exhibited a brush border was measured as an assessment of the degree of repair after R-UUO. After 6 wk of R-UUO, there was an increase in the area of kidney occupied by repaired tubules (83.7 ± 5.9%), compared with 10 d UUO kidneys (32.6 ± 7.3%). This coincided with reduced macrophage numbers, decreased hydroxyproline content, and reduced collagen accumulation and interstitial matrix expansion, compared with obstructed kidneys from UUO mice. GFR in the 6-wk R-UUO kidneys was restored to 43 to 88% of the GFR in the contralateral unobstructed kidneys. This study describes the regenerative potential of the kidney after the established interstitial matrix expansion and medullary ablation associated with UUO in the adult mouse.

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