Loss of proximal tubular transcription factor Kruppel-like factor 15 exacerbates kidney injury through loss of fatty acid oxidation.

ABSTRACT: Loss of fatty acid β-oxidation (FAO) in the proximal tubule is a critical mediator of acute kidney injury and eventual fibrosis. However, transcriptional mediators of FAO in proximal tubule injury remain understudied. Krüppel-like factor 15 (KLF15), a highly enriched zinc-finger transcription factor in the proximal tubule, was significantly reduced in proximal tubule cells after aristolochic acid I (AAI) treatment, a proximal tubule-specific injury model. Proximal tubule specific knockout of Klf15 exacerbated proximal tubule injury and kidney function decline compared to control mice during the active phase of AAI treatment, and after ischemia-reperfusion injury. Furthermore, along with worsening proximal tubule injury and kidney function decline, knockout mice exhibited increased kidney f

SUBMITTER: Piret SE 

PROVIDER: S-EPMC8608748 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature