Mechanical Stress and the Induction of Lung Fibrosis via the Midkine Signaling Pathway
Rattachement africain : cn, ca, it, de, cz. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
RATIONALE: Lung-protective ventilatory strategies have been widely used in patients with acute respiratory distress syndrome (ARDS), but the ARDS mortality rate remains unacceptably high and there is no proven pharmacologic therapy. OBJECTIVES: Mechanical ventilation can induce oxidative stress and lung fibrosis, which may contribute to high dependency on ventilator support and increased ARDS mortality. We hypothesized that the novel cytokine, midkine (MK), which can be up-regulated in oxidative stress, plays a key role in the pathogenesis of ARDS-associated lung fibrosis. METHODS: Blood samples were collected from 17 patients with ARDS and 10 healthy donors. Human lung epithelial cells were challenged with hydrogen chloride followed by mechanical stretch for 72 hours. Wild-type and MK gene-deficient (MK(-/-)) mice received two-hit injury of acid aspiration and mechanical ventilation, and were monitored for 14 days. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of MK were higher in patients with ARDS than in healthy volunteers. Exposure to mechanical stretch of lung epithelial cells led to an epithelial-mesenchymal transition profile associated with increased expression of angiotensin-converting enzyme, which was attenuated by silencing MK, its receptor Notch2, or NADP reduced oxidase 1. An increase in collagen deposition and hydroxyproline level and a decrease in lung tissue compliance seen in wild-type mice were largely attenuated in MK(-/-) mice. CONCLUSIONS: Mechanical stretch can induce an epithelial-mesenchymal transition phenotype mediated by the MK-Notch2-angiotensin-converting enzyme signaling pathway, contributing to lung remodeling. The MK pathway is a potential therapeutic target in the context of ARDS-associated lung fibrosis.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Mechanical Stress and the Induction of Lung Fibrosis via the Midkine Signaling Pathway
- Date Crossref
- 01/08/2015
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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First Affiliated Hospital of Guangzhou Medical University The State Key Laboratory of Respiratory Disease pays non établi dans la noticeÉtablissement de santé
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State Key Laboratory of Respiratory Disease pays non établi dans la noticeStructure de recherche
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Guangzhou Medical University pays non établi dans la noticeUniversité ou école supérieure
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St. Michael's Hospital pays non établi dans la noticeÉtablissement de santé
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Fondazione Ricerca Molinette pays non établi dans la noticeOrganisation à but non lucratif
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University of Turin Department of Anesthesia and Critical Care pays non établi dans la noticeUniversité ou école supérieure
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Technische Universität Dresden pays non établi dans la noticeUniversité ou école supérieure
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RWTH Aachen University pays non établi dans la noticeUniversité ou école supérieure
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Czech Academy of Sciences pays non établi dans la noticeStructure de recherche
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University of Toronto Interdepartmental Division of Critical Care Medicine pays non établi dans la noticeUniversité ou école supérieure
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Department of Anesthesiology and Intensive Care Medicine pays non établi dans la noticeInstitution
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Faculty of Medicine pays non établi dans la noticeUniversité ou école supérieure
The State Key Laboratory of Respiratory Disease — First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease et Guangzhou Medical University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.