Origin and phenotypic features of hyperplastic epithelial cells in collapsing glomerulopathy

Area of Science:

• Nephrology
• Renal Pathology
• Cell Biology

Background:

• Collapsing glomerulopathy (CG) is characterized by significant glomerular epithelial cell hyperplasia and hypertrophy.
• The origin of these hyperplastic cells in CG remains incompletely understood.
• Identifying cell origin is crucial for understanding CG pathogenesis.

Purpose of the Study:

• To investigate the phenotypic alterations of hyperplastic epithelial cells in collapsing glomerulopathy (CG).
• To determine the cellular origin of the hyperplastic and hypertrophic epithelial cells observed in CG.
• To explore the potential role of these cells in the development of glomerulosclerosis.

Main Methods:

• Immunohistochemical staining of renal biopsy specimens from two CG patients.
• Utilized markers for podocytes (PHM-5), parietal epithelial cells (PECs; cytokeratin), and cell proliferation (Ki-67).
• Analyzed cell connections, marker expression, and serial sections to assess cell origins and phenotype.

Main Results:

• Hyperplastic and hypertrophic epithelial cells in collapsed glomeruli were frequently connected to PECs and glomerular basement membranes (GBMs).
• These cells predominantly expressed cytokeratin (a PEC marker) and Ki-67 (a proliferation marker), with rare podocyte marker (PHM-5) expression.
• Serial sections indicated a potential phenotypic conversion between podocytes and PECs, with cytokeratin-positive cells associated with sclerosis.

Conclusions:

• The majority of hyperplastic and hypertrophic epithelial cells in collapsing glomerulopathy appear to originate from parietal epithelial cells (PECs).
• These PEC-derived cells may play a significant role in the characteristic glomerular tuft collapse and glomerulosclerosis seen in CG.
• Understanding the origin of these cells offers insights into CG pathogenesis and potential therapeutic targets.