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

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<sup>+</sup> 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.

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Publication Details

Journal
Ultrastructural Pathology
Published
2025-11-28
DOI
https://doi.org/10.1080/01913123.2025.2594992
Primary Topic
Renal and related cancers
Type
article
Field-Weighted Citation Impact
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article

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

Ping L. Zhang, Jamal Abukhaled, Olaf Kroneman, Sami Zarouk et al.
Ultrastructural Pathology
Renal and related cancers
article

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

Ping L. Zhang, Jamal Abukhaled, Olaf Kroneman, Sami Zarouk, Hassan Kanaan, Dilip Samarapungavan, Wěi Li, Gopal Reddy, Alexander Zarouk, Brandon D. MeCalf
article en

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<sup>+</sup> 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.

Ultrastructural PathologyVol. 50(1)
Beaumont Hospital, Royal Oak (US), Beaumont Hospital, Troy (US), Case Western Reserve University (US)
Openalex Percentile: Top 66%
Renal and related cancers
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