ArticleCommunications biology2023
Stress-responsive Gdf15 counteracts renointestinal toxicity via autophagic and microbiota reprogramming.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- UC-associated autoantibodies to αvβ6 inhibit mucosal TGFβ activation and predispose to intestinal inflammation.bioRxiv : the preprint server for biology · 2026Article
- Growth differentiation factor 15 - a new molecular target in inflammatory bowel disease: Progress and challenges.World journal of gastroenterology · 2026Article
- Convergent Roles of Growth Differentiation Factor-15 (GDF-15) in Mechanotransduction, Vascular Disorganization, and Immune Suppression in Melanoma.bioRxiv : the preprint server for biology · 2026Article
- Elevated GDF15 in ocular fluids of patients with proliferative diabetic retinopathy.Frontiers in endocrinology · 2026Article
- Evaluation of Serum and Urine GDF-15 Levels in Patients with Ureteral Stones.Diagnostics (Basel, Switzerland) · 2026Article
- The dichotomic role of cytokines in aging.Biogerontology · 2024Review
- A distinct metabolic and epigenetic state drives trained immunity in HSC-derived macrophages from autoimmune mice.Cell stem cell · 2024Article
- Leveraging Microbiome Composition Variability for Precision Medicine in Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
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 tissues and the gut barrier. An in-depth evaluation of the gut microbiota indicates that Gdf15 is associated with the abundance of mucin metabolism-linked bacteria and their enzymes. Moreover, stress-responsive Gdf15 facilitates mucin production and cellular survival via the reorganization of the autophagy regulatory network. Collectively, ISR-activated Gdf15 counteracts pathological processes via the protective reprogramming of the autophagic network and microbial community, thereby providing robust predictive biomarkers and interventions against renointestinal distress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.