Re-expression of the developmental gene Pax-2 during experimental acute tubular necrosis in mice

Background. The transcription factor Pax-2 is known to play a key regulator y role during embryonic development of the nervous and excretory systems in mammals and flies. During mouse kidney development, Pax-2 is expressed in the undifferentiated mesenchyme in response to ureter induction and continu es to be expressed in the developing comma- and s-shaped bodies. These stru ctures harbor the immediate precursors of the proximal tubular epithelial c ells. Pax-2 expression is downregulated as the differentiation of the funct ional units of the nephron proceeds. In the adult mammalian kidney, the Pax -2 protein is detectable exclusively in the epithelium of the collecting du cts. We sought to test the hypothesis that tissue regeneration is character ized by re-expression of developmentally important regulatory genes such as Pax-2. Methods. The expression pattern of Pax-2 in kidneys after experimentally-in duced acute tubular necrosis caused by intraperitoneally injected folic aci d in mice was tested by indirect immunofluorescence, Western blotting, reve rse transcriptase-polymerase chain reaction, and in situ hybridization anal ysis. Results. A transient, temporally and locally restricted reexpression of Pax -2 in regenerating proximal tubular epithelial cells was observed following kidney damage. Conclusions. These data indicate that during the regeneration processes, de velopmental paradigms may be recapitulated in order to restore mature kidne y function.