ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle.Life science alliance · 2024Trial
- Intraoperative hemidiaphragm electrical stimulation reduces oxidative stress and upregulates autophagy in surgery patients undergoing mechanical ventilation: exploratory study.Journal of translational medicine · 2016Trial
- Mitochondrial Impairment in Unloaded Postural Muscle: Mechanisms Driving Loss of Muscle Function and Mass.Antioxidants (Basel, Switzerland) · 2026Review
- Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Diaphragm Function in Health and Disease.Advances in experimental medicine and biology · 2025Review
- The molecular mechanism of sepsis-induced diaphragm dysfunction.Journal of thoracic disease · 2023Article
- Endoplasmic Reticulum Stress Contributes to Ventilator-Induced Diaphragm Atrophy and Weakness in Rats.Frontiers in physiology · 2022Article
- Angiotensin 1-7 protects against ventilator-induced diaphragm dysfunction.Clinical and translational science · 2021Article
- Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity.Antioxidants (Basel, Switzerland) · 2021Review
- [Effects of Janus kinase/signal transduction and activator of transcription 3 pathway inhibitor in skeletal muscle function in severely burned rats and its mechanism].Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns · 2021Article
- Inhibition of IL-6/JAK/STAT3 pathway rescues denervation-induced skeletal muscle atrophy.Annals of translational medicine · 2020Article
- Chaperone co-inducer BGP-15 mitigates early contractile dysfunction of the soleus muscle in a rat ICU model.Acta physiologica (Oxford, England) · 2020Article
- Disturbances in Calcium Homeostasis Promotes Skeletal Muscle Atrophy: Lessons From Ventilator-Induced Diaphragm Wasting.Frontiers in physiology · 2020Review
- Is Mitochondrial Oxidative Stress the Key Contributor to Diaphragm Atrophy and Dysfunction in Critically Ill Patients?Critical care research and practice · 2020Review
- PQQ ameliorates skeletal muscle atrophy, mitophagy and fiber type transition induced by denervation via inhibition of the inflammatory signaling pathways.Annals of translational medicine · 2019Article
- Ventilator-induced diaphragm dysfunction: translational mechanisms lead to therapeutical alternatives in the critically ill.Intensive care medicine experimental · 2019Review
- Mechanical ventilation causes diaphragm dysfunction in newborn lambs.Critical care (London, England) · 2019Article
- Mitochondrial dysfunction induces muscle atrophy during prolonged inactivity: A review of the causes and effects.Archives of biochemistry and biophysics · 2019Review
- Ventilator-induced diaphragm dysfunction in critical illness.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Role of gp130 in basal and exercise-trained skeletal muscle mitochondrial quality control.Journal of applied physiology (Bethesda, Md. : 1985) · 2018Article
Corrections and comments
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Authors and funding
34 authors at 2 institutions in 1 country.
Funding
Abstract
Controlled mechanical ventilation (CMV) is associated with the development of diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is thought to contribute significantly to delayed weaning of patients. Therefore, therapeutic strategies for preventing these processes may have clinical benefit. The aim of the current study was to investigate the role of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in CMV-mediated diaphragm wasting and weakness in rats. CMV-induced diaphragm atrophy and contractile dysfunction coincided with marked increases in STAT3 phosphorylation on both tyrosine 705 (Tyr705) and serine 727 (Ser727). STAT3 activation was accompanied by its translocation into mitochondria within diaphragm muscle and mitochondrial dysfunction. Inhibition of JAK signaling during CMV prevented phosphorylation of both target sites on STAT3, eliminated the accumulation of phosphorylated STAT3 within the mitochondria, and reversed the pathologic alterations in mitochondrial function, reduced oxidative stress in the diaphragm, and maintained normal diaphragm contractility. In addition, JAK inhibition during CMV blunted the activation of key proteolytic pathways in the diaphragm, as well as diaphragm atrophy. These findings implicate JAK/STAT3 signaling in the development of diaphragm muscle atrophy and dysfunction during CMV and suggest that the delayed extubation times associated with CMV can be prevented by inhibition of Janus kinase signaling.-Smith, I. J., Godinez, G. L., Singh, B. K., McCaughey, K. M., Alcantara, R. R., Gururaja, T., Ho, M. S., Nguyen, H. N., Friera, A. M., White, K. A., McLaughlin, J. R., Hansen, D., Romero, J. M., Baltgalvis, K. A., Claypool, M. D., Li, W., Lang, W., Yam, G. C., Gelman, M. S., Ding, R., Yung, S. L., Creger, D. P., Chen, Y., Singh, R., Smuder, A. J., Wiggs, M. P., Kwon, O.-S., Sollanek, K. J., Powers, S. K., Masuda, E. S., Taylor, V. C., Payan, D. G., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.
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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.