NORMAL TUBULAR REGENERATION AND DIFFERENTIATION OF THE POSTISCHEMIC KIDNEY IN MICE LACKING VIMENTIN

Proliferation and dedifferentiation of tubular cells are the hallmark of early regeneration after renal ischemic injury, Vimentin, a class I II intermediate filament expressed only in mesenchymal cells of mature mammals, was shown to be transiently expressed in post-ischemic renal tubular epithelial cells, Vimentin re-expression was interpreted as a marker of cellular dedifferentiation, but its role in tubular regener ation after renal ischemia has also been hypothesized This role was ev aluated in mice bearing a null mutation of the vimentin gene. Expressi on of vimentin, proliferating cell nuclear antigen (a marker of cellul ar proliferation), and villin (a marker of differentiated brush-border membranes) was studied in wild-type (Vim(+/+)), heterozygous (Vim(+/- )), and homozygous (Vim(-/-)) mice subjected to transient ischemia of the left kidney. As expected, vimentin was detected by immunohistochem istry at the basal pole of proximal tubular cells from post-ischemic k idney in Vim(+/+) and Vim(+/-) mice from day, 2 to day 28, The express ion of the reporter gene beta-galactosidase in Vim(+/-) and Vim(-/-) m ice confirmed the tubular origin of vimentin. No compensatory expressi on of keratin could be demonstrated ill Vim(-/-) mice, The intensity o f proliferating cell nuclear antigen labeling and the pattern of villi n expression were comparable in Vim(-/-)Vim(+/-) and Vim(+/+) mice at any time of the study. After 60 days, the structure of post-ischemic k idneys in Vim(-/-) mice was indistinguishable from that of normal non- operated kidneys in Vim(+/+) mice, In conclusion, 1) the pattern of po st-ischemic proximal tubular cell proliferation, differentiation, and tubular organization was not impaired in mice lacking vimentin and 2) these results suggest that the transient tubular expression of vimenti n is not instrumental in tubular regeneration after renal ischemic inj ury.