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

Abstract

Background. The transcription factor Pax-2 is known to play a key regulatory 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 continues to be expressed in the developing comma- and s-shaped bodies. These structures harbor the immediate precursors of the proximal tubular epithelial cells. Pax-2 expression is downregulated as the differentiation of the functional units of the nephron proceeds. In the adult mammalian kidney, the Pax-2 protein is detectable exclusively in the epithelium of the collecting ducts. We sought to test the hypothesis that tissue regeneration is characterized by re-expression of developmentally important regulatory genes such as Pax-2. Methods. The expression pattern of Pax-2 in kidneys after experimentally-induced acute tubular necrosis caused by intraperitoneally injected folic acid in mice was tested by indirect immunofluorescence, Western blotting, reverse transcriptase-polymerase chain reaction, and in situ hybridization analysis. 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, developmental paradigms may be recapitulated in order to restore mature kidney function.