Trial reportSkeletal muscle2018
HIF prolyl hydroxylase inhibition protects skeletal muscle from eccentric contraction-induced injury.
Trial report in Skeletal muscle, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
What it found
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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
9 citing papers in PubMed, 32 citations in OpenAlex.
- Hypoxia and Tissue Regeneration: Adaptive Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Macrophage immunometabolism: emerging targets for regrowth in aging muscle.American journal of physiology. Endocrinology and metabolism · 2025Review
- Mineralocorticoid receptor antagonists and glucocorticoids differentially affect skeletal muscle inflammation and pathology in muscular dystrophy.JCI insight · 2022Article
- Effect of chronic intermittent hypoxia (CIH) on neuromuscular junctions and mitochondria in slow- and fast-twitch skeletal muscles of mice-the role of iNOS.Skeletal muscle · 2022Article
- Hypoxia-inducible factors and diabetes.The Journal of clinical investigation · 2020Review
- HIF-hypoxia signaling in skeletal muscle physiology and fibrosis.Journal of cell communication and signaling · 2020Review
- Angiotensin-converting-enzyme inhibitor prevents skeletal muscle fibrosis in myocardial infarction mice.Skeletal muscle · 2020Article
- Prolyl hydroxylase domain 2 reduction enhances skeletal muscle tissue regeneration after soft tissue trauma in mice.PloS one · 2020Article
- Correction to: HIF prolyl hydroxylase inhibition protects skeletal muscle from eccentric contraction induced injury.Skeletal muscle · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn muscular dystrophy and old age, skeletal muscle repair is compromised leading to fibrosis and fatty tissue accumulation. Therefore, therapies that protect skeletal muscle or enhance repair would be valuable medical treatments. Hypoxia-inducible factors (HIFs) regulate gene transcription under conditions of low oxygen, and HIF target genes EPO and VEGF have been associated with muscle protection and repair. We tested the importance of HIF activation following skeletal muscle injury, in both a murine model and human volunteers, using prolyl hydroxylase inhibitors that stabilize and activate HIF.
methodsUsing a mouse eccentric limb injury model, we characterized the protective effects of prolyl hydroxylase inhibitor, GSK1120360A. We then extended these studies to examine the impact of EPO modulation and infiltrating immune cell populations on muscle protection. Finally, we extended this study with an experimental medicine approach using eccentric arm exercise in untrained volunteers to measure the muscle-protective effects of a clinical prolyl hydroxylase inhibitor, daprodustat.
resultsGSK1120360A dramatically prevented functional deficits and histological damage, while accelerating recovery after eccentric limb injury in mice. Surprisingly, this effect was independent of EPO, but required myeloid HIF1α-mediated iNOS activity. Treatment of healthy human volunteers with high-dose daprodustat reduced accumulation of circulating damage markers following eccentric arm exercise, although we did not observe any diminution of functional deficits with compound treatment.
conclusionThe results of these experiments highlight a novel skeletal muscle protective effect of prolyl hydroxylase inhibition via HIF-mediated expression of iNOS in macrophages. Partial recapitulation of these findings in healthy volunteers suggests elements of consistent pharmacology compared to responses in mice although there are clear differences between these two systems.
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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.