The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy

Nicole K. Andeen, Tri Q. Nguyen, Floor Steegh, Kelly L. Hudkins, Behzad Najafian, Charles E. Alpers

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (PECs) (claudin-1), and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman's capsule in controls, but significantly increased in histologically early DN. Ki-67-expressing cells were identified on the glomerular tuft and Bowman's capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration.

Original languageEnglish (US)
Pages (from-to)1099-1107
Number of pages9
JournalKidney International
Volume88
Issue number5
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Keywords

  • Diabetic nephropathy
  • Immunophenotype
  • Parietal epithelial cell
  • Podocyte
  • Progenitor cell

ASJC Scopus subject areas

  • Nephrology

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