Abstract
Aim: The goal of this study was to examine the capacity for glomerular repair after a podocyte-depleting injury. Methods: We created transgenic (TG) mice expressing the yeast enzyme cytosine deaminase specifically in glomerular podocytes. In these TG animals, the prodrug 5-flucytosine (5-FC) is converted to 5-fluorouracil and promotes cell death. Results: Treatment with increasing dosages of 5-FC caused graded increases in proteinuria 1-2 weeks after treatment, which returned to control levels by the 10-week time point. Light microscopic examination revealed minimal pathology at the 2-week time point, but electron microscopy revealed found foot process effacement as well as focal areas of glomerular basement membrane duplication, and immunohistochemical studies detected podocyte apoptosis and a decrease in the number of Wilms' tumor protein 1 (WT1)-positive cells. By the 10-week time point, however, the number of WT1-positive cells was similar to controls and a few mice had developed focal areas of glomerulosclerosis. Consistent with the effects of 5-FC on podocyte number, expression of the podocyte mRNAs for nephrin, podocin, synaptopodin and podocalyxin were altered in a similar temporal fashion. Conclusion: The glomerulus has a significant capacity for repair after a podocyte-depleting injury.
Original language | English (US) |
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Pages (from-to) | e10-e22 |
Journal | Nephron - Experimental Nephrology |
Volume | 121 |
Issue number | 1-2 |
DOIs | |
State | Published - Dec 2012 |
Keywords
- Glomerular disease
- Mouse model
- Podocyte
ASJC Scopus subject areas
- Nephrology
- Physiology
- Genetics