Observational studyThorax2015
Increased expression of GDF-15 may mediate ICU-acquired weakness by down-regulating muscle microRNAs.
Observational study in Thorax, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 3 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Circulating biomarkers in older adults with and without sarcopenia: a systematic review and meta-analysis.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Pooled it
- Growth differentiation factor-15 as a biomarker for intensive care unit-acquired weakness: a meta-analysis.Frontiers in medicine · 2025Pooled it
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Biomarkers of Cellular Senescence Predict the Onset of Mobility Disability and Are Reduced by Physical Activity in Older Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Trial
- DNA methylation alterations in muscle of critically ill patients.Journal of cachexia, sarcopenia and muscle · 2022Trial
- Effects of elastic band resistance training and nutritional supplementation on muscle quality and circulating muscle growth and degradation factors of institutionalized elderly women: the Vienna Active Ageing Study (VAAS).European journal of applied physiology · 2016Trial
- Muscle Dysfunction in Critical Illness: Established Mechanisms and the Potential Contribution of the NLRP3 Inflammasome.International journal of molecular sciences · 2026Review
- Critical illness impairs coordinated myogenesis: a prospective longitudinal study of skeletal muscle progenitor cell biology using serial muscle biopsies (SATELLITE study).Critical care (London, England) · 2026Observational
- ICU-Acquired Weakness: An Unsolved Clinical Problem: A Narrative Review.Journal of clinical medicine · 2026Review
- Frailty Exacerbates Disability in Progressive Multiple Sclerosis.Annals of clinical and translational neurology · 2026Article
- Serum Gelsolin Combined with Albumin Might Be a Promising Marker for the Intensive Care Unit-Acquired Weakness-A Pilot Study.Diagnostics (Basel, Switzerland) · 2026Article
- Pleiotropic effects of GDF-15 to regulate nutritional status: perspectives from body composition to nutrition-related disorders.British journal of biomedical science · 2026Review
- Phase Angle Shows a Negative Correlation With Serum GDF-15 Concentrations in Hospitalized Patients With Cardiovascular Disease.Journal of nutrition and metabolism · 2026Article
- Mitochondrial Dysfunction Contributes to Sustained Muscle Loss After Cardiac Surgery: A Prospective Observational Study.Journal of cachexia, sarcopenia and muscle · 2025Observational
- Identification of Anticancer Target Combinations to Treat Pancreatic Cancer and Its Associated Cachexia Using Constraint-Based Modeling.Molecules (Basel, Switzerland) · 2025Article
- Cisplatin-Induced Muscle Wasting and Atrophy: Molecular Mechanism and Potential Therapeutic Interventions.Journal of cachexia, sarcopenia and muscle · 2025Review
- Longitudinal Assessment of Blood-Based Inflammatory, Neuromuscular, and Neurovascular Biomarker Profiles in Intensive Care Unit-Acquired Weakness: A Prospective Single-Center Cohort Study.Neurocritical care · 2025Observational
- Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- Targeting the GDF15 Signalling for Obesity Treatment: Recent Advances and Emerging Challenges.Journal of cellular and molecular medicine · 2024Review
- MicroRNA Expression Profile in Patients Admitted to ICU as Novel and Reliable Approach for Diagnostic and Therapeutic Purposes.Molecular biotechnology · 2024Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleThe molecular mechanisms underlying the muscle atrophy of intensive care unit-acquired weakness (ICUAW) are poorly understood. We hypothesised that increased circulating and muscle growth and differentiation factor-15 (GDF-15) causes atrophy in ICUAW by changing expression of key microRNAs.
objectivesTo investigate GDF-15 and microRNA expression in patients with ICUAW and to elucidate possible mechanisms by which they cause muscle atrophy in vivo and in vitro.
methodsIn an observational study, 20 patients with ICUAW and seven elective surgical patients (controls) underwent rectus femoris muscle biopsy and blood sampling. mRNA and microRNA expression of target genes were examined in muscle specimens and GDF-15 protein concentration quantified in plasma. The effects of GDF-15 on C2C12 myotubes in vitro were examined. MEASUREMENTS AND MAIN
resultsCompared with controls, GDF-15 protein was elevated in plasma (median 7239 vs 2454 pg/mL, p=0.001) and GDF-15 mRNA in the muscle (median twofold increase p=0.006) of patients with ICUAW. The expression of microRNAs involved in muscle homeostasis was significantly lower in the muscle of patients with ICUAW. GDF-15 treatment of C2C12 myotubes significantly elevated expression of muscle atrophy-related genes and down-regulated the expression of muscle microRNAs. miR-181a suppressed transforming growth factor-β (TGF-β) responses in C2C12 cells, suggesting increased sensitivity to TGF-β in ICUAW muscle. Consistent with this suggestion, nuclear phospho-small mothers against decapentaplegic (SMAD) 2/3 was increased in ICUAW muscle.
conclusionsGDF-15 may increase sensitivity to TGF-β signalling by suppressing the expression of muscle microRNAs, thereby promoting muscle atrophy in ICUAW. This study identifies both GDF-15 and associated microRNA as potential therapeutic targets.
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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.