Stress-responsive Gdf15 counteracts renointestinal toxicity via autophagic and microbiota reprogramming.

ABSTRACT: The integrated stress response (ISR) plays a pivotal role in the cellular stress response, primarily through global translational arrest and the upregulation of cellular adaptation-linked molecules. Growth differentiation factor 15 (Gdf15) is a potent stress-responsive biomarker of clinical inflammatory and metabolic distress in various types of diseases. Herein, we assess whether ISR-driven cellular stress contributes to pathophysiological outcomes by modulating Gdf15. Clinical transcriptome analysis demonstrates that PKR is positively associated with Gdf15 expression in patients with renal injury. Gdf15 expression is dependent on protein kinase R (PKR)-linked ISR during acute renointestinal distress in mice and genetic ablation of Gdf15 aggravates chemical-induced lesions in renal tissue

SUBMITTER: Ray N 

PROVIDER: S-EPMC10239500 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature