NDLI: Serine/threonine kinase-protein kinase B and extracellular signal-regulated kinase regulate ventilator-induced pulmonary fibrosis after bleomycin-induced acute lung injury: a prospective, controlled animal experiment

Content Provider	Springer Nature : BioMed Central
Author	Li, Li-Fu Liao, Shuen-Kuei Huang, Chung-Chi Hung, Ming-Jui Quinn, Deborah A
Abstract	Introduction Lung fibrosis, reduced lung compliance, and severe hypoxemia found in patients with acute lung injury often result in a need for the support of mechanical ventilation. High-tidal-volume mechanical ventilation can increase lung damage and fibrogeneic activity but the mechanisms regulating the interaction between high tidal volume and lung fibrosis are unclear. We hypothesized that high-tidal-volume ventilation increased pulmonary fibrosis in acute lung injury via the serine/threonine kinase-protein kinase B (Akt) and mitogen-activated protein kinase pathways. Methods After 5 days of bleomycin administration to simulate acute lung injury, male C57BL/6 mice, weighing 20 to 25 g, were exposed to either high-tidal-volume mechanical ventilation (30 ml/kg) or low-tidal-volume mechanical ventilation (6 ml/kg) with room air for 1 to 5 hours. Results High-tidal-volume ventilation induced type I and type III procollagen mRNA expression, microvascular permeability, hydroxyproline content, Masson's trichrome staining, S100A4/fibroblast specific protein-1 staining, activation of Akt and extracellular signal-regulated kinase (ERK) 1/2, and production of macrophage inflammatory protein-2 and 10 kDa IFNγ-inducible protein in a dose-dependent manner. High-tidal-volume ventilation-induced lung fibrosis was attenuated in Akt-deficient mice and in mice with pharmacologic inhibition of ERK1/2 activity by PD98059. Conclusion We conclude that high-tidal-volume ventilation-induced microvascular permeability, lung fibrosis, and chemokine production were dependent, in part, on activation of the Akt and ERK1/2 pathways.
Related Links	https://ccforum.biomedcentral.com/counter/pdf/10.1186/cc6983.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	13648535
DOI	10.1186/cc6983
Journal	Critical Care
Issue Number	4
Volume Number	12
Language	English
Publisher	BioMed Central
Publisher Date	2008-08-09
Access Restriction	Open
Subject Keyword	Intensive Critical Care Medicine Emergency Medicine Acute Lung Injury Pulmonary Fibrosis Acute Respiratory Distress Syndrome PD98059 Evans Blue
Content Type	Text
Resource Type	Article
Subject	Critical Care and Intensive Care Medicine
Journal Impact Factor	8.8/2023
5-Year Journal Impact Factor	10.4/2023

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