The Intermediate Filament Nestin is Highly Expressed in Normal Human Podocytes and Podocytes in Glomerular Disease

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Abstract
The intermediate protein nestin is expressed in proliferating embryonic tissues and adult tissues undergoing repair. Recently this protein been identified in rodent podocytes. Its role in this cell is unknown, since podocytes are believed to be terminally differentiated and nondividing. We report the first study of nestin in human kidney. Nestin expression in normal mature human glomeruli was confined to podocytes. In developing kidney, nestin was detected in metanephric blastema and in podocytic cells at all stages of glomerular development. Nestin co-localized with vimentin but not with actin or heavy chain myosin IIA, using a mouse podocyte cell line. Knockdown of nestin in a murine podocyte cell line failed to produce any obvious phenotypic change or alteration in vimentin distribution but was associated with increased cell cycling. A survey of glomerular diseases failed to identify any condition lacking nestin, indicating that the protein is critical for some aspect of podocyte function. Perhaps through an association with vimentin, nestin serves to bolster the mechanical strength of these cells that experience high tensile stress during glomerular filtration. Nestin was also expressed in podocytes that are reported to be ‘dysregulated’ (lacking podocyte markers). Thus, nestin has a potential as a reliable podocyte marker, even for podocytes that are not completely differentiated (for example, during development) or ‘dedifferentiated’ in glomerular disease.