ArticleScientific reports2017
Smad3 initiates oxidative stress and proteolysis that underlies diaphragm dysfunction during mechanical ventilation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- A preclinical rat model for bilateral phrenic nerve stimulation during mechanical ventilation.Animal models and experimental medicine · 2026Article
- Chronic sublethal exposure to methylmercury lengthens telomeres in developing zebra finches.Environmental pollution (Barking, Essex : 1987) · 2025Article
- Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.PloS one · 2025Article
- Involvement of Phosphate and the Consequences of Its High Consumption in Energy Metabolism and Muscle Functions.Journal of nutrition and metabolism · 2025Review
- Diaphragm Function in Health and Disease.Advances in experimental medicine and biology · 2025Review
- Diverse roles of SARS-CoV-2 Spike and Nucleocapsid proteins in EndMT stimulation through the TGF-β-MRTF axis inhibited by aspirin.Cell communication and signaling : CCS · 2024Article
- Aberrant mitochondrial dynamics contributes to diaphragmatic weakness induced by mechanical ventilation.PNAS nexus · 2023Article
- Small-Molecule Inhibition of MuRF1 Prevents Early Disuse-Induced Diaphragmatic Dysfunction and Atrophy.International journal of molecular sciences · 2023Article
- Impact of cancer cachexia on respiratory muscle function and the therapeutic potential of exercise.The Journal of physiology · 2022Review
- Endoplasmic Reticulum Stress Contributes to Ventilator-Induced Diaphragm Atrophy and Weakness in Rats.Frontiers in physiology · 2022Article
- Metabolomic Profiling of Respiratory Muscles and Lung in Response to Long-Term Controlled Mechanical Ventilation.Frontiers in cell and developmental biology · 2022Article
- Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation.Oxidative medicine and cellular longevity · 2021Article
- Superoxide-mediated oxidative stress accelerates skeletal muscle atrophy by synchronous activation of proteolytic systems.GeroScience · 2020Article
- Is Mitochondrial Oxidative Stress the Key Contributor to Diaphragm Atrophy and Dysfunction in Critically Ill Patients?Critical care research and practice · 2020Review
- Disturbances in Calcium Homeostasis Promotes Skeletal Muscle Atrophy: Lessons From Ventilator-Induced Diaphragm Wasting.Frontiers in physiology · 2020Review
- Article
- 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
- Hemorrhagic Shock Sensitized the Diaphragm to Ventilator-Induced Dysfunction through the Activation of IL-6/JAK/STAT Signaling-Mediated Autophagy in Rats.Mediators of inflammation · 2019Article
- Serum iron levels are an independent predictor of in-hospital mortality of critically ill patients: a retrospective, single-institution study.The Journal of international medical research · 2019Article
- Ventilator-induced diaphragm dysfunction in critical illness.Experimental biology and medicine (Maywood, N.J.) · 2018Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
Prolonged use of mechanical ventilation (MV) leads to atrophy and dysfunction of the major inspiratory muscle, the diaphragm, contributing to ventilator dependence. Numerous studies have shown that proteolysis and oxidative stress are among the major effectors of ventilator-induced diaphragm muscle dysfunction (VIDD), but the upstream initiator(s) of this process remain to be elucidated. We report here that periodic diaphragm contraction via phrenic nerve stimulation (PNS) substantially reduces MV-induced proteolytic activity and oxidative stress in the diaphragm. We show that MV rapidly induces phosphorylation of Smad3, and PNS nearly completely prevents this effect. In cultured cells, overexpressed Smad3 is sufficient to induce oxidative stress and protein degradation, whereas inhibition of Smad3 activity suppresses these events. In rats subjected to MV, inhibition of Smad3 activity by SIS3 suppresses oxidative stress and protein degradation in the diaphragm and prevents the reduction in contractility that is induced by MV. Smad3's effect appears to link to STAT3 activity, which we previously identified as a regulator of VIDD. Inhibition of Smad3 suppresses STAT3 signaling both in vitro and in vivo. Thus, MV-induced diaphragm inactivity initiates catabolic changes via rapid activation of Smad3 signaling. An early intervention with PNS and/or pharmaceutical inhibition of Smad3 may prevent clinical VIDD.
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