Glomerular epithelial cell differentiation and aberration evaluated using PAX8 and WT1 immunostains

Ultrastruct Pathol. 2026;50(1):82-91. doi: 10.1080/01913123.2025.2594992. Epub 2025 Nov 28.

Abstract

Paired box 8 (PAX8) and Wilms' tumor 1 (WT1) of cap mesenchyme play important roles in tubular epithelial transition and podocyte maturation of the kidney. Parietal epithelial cells (PEC) progenitors demonstrate activity of these two factors in mature glomeruli. PECs can be activated into spindle cell crescents in crescentic glomerulonephritis (CreGN) or into podocyte hyperplasia in collapsing glomerulopathy (ColGN) based on histologic evidence. The study aimed to use PAX8 and WT1 stains to demonstrate the two transitional processes of mesonephros/metanephros and aberrant in CreGN, and ColGN. Immunohistochemical (IHC) stains for both PAX8 and WT1 were performed in fetal mesonephros/metanephros, adult negative controls, CreGN, and ColGN. Expressive patterns of PAX8 and WT1 in mesonephros/early fetal kidneys, adult kidneys, and aberrant glomerular changes were evaluated. PAX8 showed continuous nuclear expression in the parietal epithelium of mesonephros/metanephros, adult kidneys, & primordial podocytes, and consistent positivity in all renal tubules. WT1 showed strong nuclear and cytoplasmic expression within mature podocytes at all stages, despite some staining of WT1 in parietal epithelium. Cellular crescents and hyperplastic podocytes were strongly positive for PAX8, and only weakly positive in the nuclei of WT1. Our data support that PAX8+ PEC involve in mesenchymal-epithelial transition (MET) in renal tubules, a possible induction of early podocyte development, and aberrant epithelial proliferation of CreGN and ColGN. In addition, WT1 is fully devoted to podocyte maturation and is also partially involved in the aberrant epithelial proliferation of the two glomerular diseases.

Keywords: Collapsing glomerulopathy; PAX8; WT-1; focal segmental glomerulosclerosis; parietal epithelium; progenitor cells; proliferative podocytes.

MeSH terms

  • Cell Differentiation* / physiology
  • Epithelial Cells* / metabolism
  • Epithelial Cells* / pathology
  • Epithelial Cells* / ultrastructure
  • Glomerulonephritis* / metabolism
  • Glomerulonephritis* / pathology
  • Humans
  • Immunohistochemistry
  • Kidney Glomerulus* / pathology
  • Mesonephros / pathology
  • PAX8 Transcription Factor* / analysis
  • Podocytes / pathology
  • WT1 Proteins* / analysis
  • WT1 Proteins* / metabolism

Substances

  • PAX8 Transcription Factor
  • WT1 Proteins
  • PAX8 protein, human
  • WT1 protein, human