Podocyte-specific KLF4 is required to maintain parietal epithelial cell quiescence in the kidney.

ABSTRACT: Podocyte loss triggering aberrant activation and proliferation of parietal epithelial cells (PECs) is a central pathogenic event in proliferative glomerulopathies. Podocyte-specific Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, is essential for maintaining podocyte homeostasis and PEC quiescence. Using mice with podocyte-specific knockdown of Klf4, we conducted glomerular RNA-sequencing, tandem mass spectrometry, and single-nucleus RNA-sequencing to identify cell-specific transcriptional changes that trigger PEC activation due to podocyte loss. Integration with in silico chromatin immunoprecipitation identified key ligand-receptor interactions, such as fibronectin 1 (FN1)–αVβ6, between podocytes and PECs dependent on KLF4 and downstream signal transducer and activator o

SUBMITTER: Pace JA 

PROVIDER: S-EPMC8442927 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature