ATF4 in proximal tubules modulates kidney function and modifies the metabolome.

ABSTRACT: Activating transcription factor 4 (ATF4) is a transcription factor that mediates the response to stress at the cellular, tissue, and organism level. We deleted the gene encoding ATF4 in the proximal tubules of the mouse kidney by using a temporal and cell type-specific approach. We show that ATF4 plays a major role in regulating the transcriptome and proteome, which, in turn, influences the metabolome and kidney functions. Genome-wide transcriptomics and single-plot, solid-phase-enhanced sample preparation (SP3)-proteomics studies reveal that ATF4 deletion changes more than 30% of transcripts and, similarly, corresponding proteins in the proximal tubules. Gene Set Enrichment Analysis indicates major changes in transporters, including amino acid transporters. Metabolomic analyses show that

SUBMITTER: Chi Y 

PROVIDER: S-EPMC12343659 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature