Parietal epithelial cell differentiation to a podocyte fate in the aged mouse kidney

Natalya V. Kaverina, Diana G. Eng, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Healthy aging is typified by a progressive and absolute loss of podocytes over the lifespan of animals and humans. To test the hypothesis that a subset of glomerular parietal epithelial cell (PEC) progenitors transition to a podocyte fate with aging, dual reporter PEC-rtTA|LC1|tdTomato|Nphs1-FLPo|FRT-EGFP mice were generated. PECs were inducibly labeled with a tdTomato reporter, and podocytes were constitutively labeled with an EGFP reporter. With advancing age (14 and 24 months) glomeruli in the juxta-medullary cortex (JMC) were more severely injured than those in the outer cortex (OC). In aged mice (24m), injured glomeruli with lower podocyte number (41% decrease), showed more PEC migration and differentiation to a podocyte fate than mildly injured or healthy glomeruli. PECs differentiated to a podocyte fate had ultrastructural features of podocytes and co-expressed the podocyte markers podocin, nephrin, p57 and VEGF164, but not markers of mesangial (Perlecan) or endothelial (ERG) cells. PECs differentiated to a podocyte fate did not express CD44, a marker of PEC activation. Taken together, we demonstrate that a subpopulation of PECs differentiate to a podocyte fate predominantly in injured glomeruli in mice of advanced age.

Original languageEnglish
Pages (from-to)1-24
Number of pages24
JournalAging
Volume12
Issue number17
DOIs
StatePublished - 2020

Keywords

  • Bowman's capsule
  • Differentiation
  • EGFP
  • Reporter
  • tdTomato

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