NFATc1 identifies a population of proximal tubule cell progenitors

Melissa Langworthy, Bin Zhou, Mark De Caestecker, Gilbert Moeckel, H. Scott Baldwin

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Recovery from acute kidney injury requires regeneration of tubule cells. Because calcineurin induces nuclear transport of NFATc proteins, whose expression pattern correlates with the nephron segments injured by calcineurin inhibitors, we hypothesized that NFATcl plays a role in modifying epithelial regeneration after injury. To test this, we induced proximal tubular cell (PTC) injury in Balb/c mice and Nfatc1 +/- mice with mercuric chloride; the PTCs of Nfatc1 +/- mice demonstrated increased apoptosis, sustained injury, and delayed regeneration. To attenuate NFATcl activity further, we injected cyclosporin A daily. Cyclosporin A-treated Nfatc1 +/- mice demonstrated rapid and severe injury after administration of mercuric chloride, with increased serum creatinine, increased apoptosis, decreased PTC proliferation, and increased mortality compared with similarly treated wild-type mice. Using a novel NFATcl transgenic line that reports activation of an NFATcl enhancer domain critical for NFATcl autoamplification, we demonstrated accentuated NFATcl expression in a PTC subpopulation after mercuric chloride-induced injury. In addition, NFATcl-labeled, apoptosis-resistant PTCs proliferated to repair the damaged proximal tubule segment. These data provide evidence for a resident progenitor PTC population and suggest a role for NFATcl in the regeneration of injured proximal tubules.

Original languageEnglish (US)
Pages (from-to)311-321
Number of pages11
JournalJournal of the American Society of Nephrology
Volume20
Issue number2
DOIs
StatePublished - Feb 2009
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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