Foxc1 and Foxc2 are necessary to maintain glomerular podocytes

Masaru Motojima*, Tsutomu Kume, Taiji Matsusaka

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Foxc1 and Foxc2 (Foxc1/2) are transcription factors involved in many biological processes. In adult kidneys, expression of Foxc1/2 is confined to the glomerular epithelial cells, i.e., podocytes. To bypass embryonic lethality of Foxc1/2 null mice, mice ubiquitously expressing inducible-Cre (ROSA26-CreERT2) or mice expressing Cre in podocytes (Nephrin-Cre) were mated with floxed-Foxc1 and floxed-Foxc2 mice. The CreERT2 was activated in adult mice by administrations of tamoxifen. Eight weeks after tamoxifen treatment, ROSA26-CreERT2; Foxc1+/flox; Foxc2flox/flox mice developed microalbuminuria, while ROSA26-Cre ERT2; Foxc1flox/flox; Foxc2+/flox mice had no microalbuminuria. The kidneys of conditional-Foxc1/2 null mice showed proteinaceous casts, protein reabsorption droplets in tubules and huge vacuoles in podocytes, indicating severe podocyte injury and massive proteinuria. Comparison of gene expression profiles revealed that Foxc1/2 maintain expression of genes necessary for podocyte function such as podocin and Cxcl12. In addition, mice with an innate podocyte-specific deletion of Foxc1/2 by Nephrin-Cre develop similar podocyte injury. These results demonstrate dose-dependence of Foxc1/2 gene in maintaining the podocyte with a more critical role for Foxc2 than Foxc1 and a critical role of Foxc1/2 in regulating expression of genes that maintain podocyte integrity.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalExperimental Cell Research
Volume352
Issue number2
DOIs
Publication statusPublished - Mar 15 2017

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Keywords

  • FSGS
  • Foxc1
  • Foxc2
  • Podocyte
  • Proteinuria

ASJC Scopus subject areas

  • Cell Biology

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