Inhibition of forkhead boxO-specific transcription prevents mechanical ventilation-induced diaphragm dysfunction

Critical Care Medicine
Ashley J SmuderS K Powers

Abstract

Mechanical ventilation is a lifesaving measure for patients with respiratory failure. However, prolonged mechanical ventilation results in diaphragm weakness, which contributes to problems in weaning from the ventilator. Therefore, identifying the signaling pathways responsible for mechanical ventilation-induced diaphragm weakness is essential to developing effective countermeasures to combat this important problem. In this regard, the forkhead boxO family of transcription factors is activated in the diaphragm during mechanical ventilation, and forkhead boxO-specific transcription can lead to enhanced proteolysis and muscle protein breakdown. Currently, the role that forkhead boxO activation plays in the development of mechanical ventilation-induced diaphragm weakness remains unknown. This study tested the hypothesis that mechanical ventilation-induced increases in forkhead boxO signaling contribute to ventilator-induced diaphragm weakness. University research laboratory. Young adult female Sprague-Dawley rats. Cause and effect was determined by inhibiting the activation of forkhead boxO in the rat diaphragm through the use of a dominant-negative forkhead boxO adeno-associated virus vector delivered directly to the diaphragm. O...Continue Reading

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Citations

Dec 3, 2015·Current Opinion in Critical Care·Basil J Petrof, Sabah N Hussain
Apr 8, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Li-Fu LiYung-Yang Liu
Apr 1, 2016·Journal of Cachexia, Sarcopenia and Muscle·David BergerJoerg C Schefold
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May 17, 2018·American Journal of Respiratory Cell and Molecular Biology·Huibin Tang, Joseph B Shrager
Apr 12, 2019·Journal of Cachexia, Sarcopenia and Muscle·Ashley J SmuderScott K Powers
Jan 17, 2020·Antioxidants & Redox Signaling·Scott K PowersHayden Hyatt
Dec 25, 2019·Respiratory Research·Tatsutoshi ShimataniRobinder G Khemani
Nov 21, 2018·Experimental Biology and Medicine·Yung-Yang Liu, Li-Fu Li
Jul 28, 2019·Intensive Care Medicine Experimental·Oscar PeñuelasJosé Ángel Lorente
Nov 20, 2018·Archives of Biochemistry and Biophysics·Hayden HyattScott K Powers

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