Phenotypic change of glomerular podocytes in primary focal segmental glomerulosclerosis: developmental paradigm?

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Abstract
WT1 and Pax2 are transcription factors involved in kidney development and phenotypic regulation of glomerular epithelial cells. In primary focal segmental glomerulosclerosis (FSGS), the alteration of the podocyte is important for the development of the cellular lesion (CL) and glomerular scar formation. To investigate the contribution of WT1 and Pax2 to the development of the CL in primary FSGS, immunohistological studies were performed using renal biopsy specimens on the expression of WT1, Pax2 and cytokeratin (CK), which is an epithelial marker but never found in normal podocytes. The expression of WT1 was decreased in the CL compared with unaffected podocytes, but Pax2 and CK were expressed significantly in the CL and also in the cells morphologically recognized as podocytes in cases with CL. Our results suggest that re‐expression of Pax2 resulting in phenotypic change of podocytes to a different epithelial form is important for the development of the CL in primary FSGS. Normal podocytes resemble mesenchymal cells since they express both vimentin and WT1. In contrast, epithelial cells including parietal epithelial cells of the Bowman's capsule express both Pax2 and CK. Therefore, the mechanism of phenotypic change of podocytes in the CL in primary FSGS might be mesenchymal–epithelial transformation and a developmental paradigm.

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