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Phosphoproteome profiling provides insight into the mechanisms of ventilator-induced lung injury.

ABSTRACT: The incidence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common health problem in the clinic and is projected to increase in prevalence in the future. Mechanical ventilation is commonly used to provide respiratory support and has become indispensable in emergency and critical medicine. However, ventilator use can result in lung tissue damage, collectively termed ventilator-induced lung injury (VILI). In the present study, phosphoprotein profiling of blood and tissue samples from ventilated and non-ventilated mice was performed and key changes in protein levels and cell signaling during VILI were identified. Activation of the PI3K/AKT and mitogen activated protein kinase signaling pathways, in addition to changes in expression of cancer, inflammatory and cell-death related proteins were detected in response to mechanical ventilation. Focal adhesion-related protein levels and signaling pathways were also significantly altered in an injury model compared with control. VILI can affect patient mortality in ALI and ARDS cases, and no targeted treatment options currently exist. Identifying biomarkers and understanding the signaling pathways associated with VILI is critical for the development of future therapies.

SUBMITTER: Ren R

PROVIDER: S-EPMC7185165 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Phosphoproteome profiling provides insight into the mechanisms of ventilator-induced lung injury.

Ren Rongrong R Ruan Zhengshang Z Ding Haoshu H Du Junming J Yu Weifeng W

Experimental and therapeutic medicine 20200401 6

The incidence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common health problem in the clinic and is projected to increase in prevalence in the future. Mechanical ventilation is commonly used to provide respiratory support and has become indispensable in emergency and critical medicine. However, ventilator use can result in lung tissue damage, collectively termed ventilator-induced lung injury (VILI). In the present study, phosphoprotein profiling of blood and ...[more]

PMID: 32346427

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Project description:In this model of ventilator-induced lung injury (VILI), we compared the gene expression profile of whole lungs extracted from sponaneously breathing mice (control, c) or mouse submitted to 8 hours mechanical venitlation with 12 ml/kg tidal volume 2cmH2O of positive end expiratory pressure (PEEP) (ventilation, v). Spontaneously breathing NOD/shi mice were randomized to control (n=3) or ventilation (n=5) condition. In brief, mice were anesthetized with the injection of ketamine (65 mg/kg, ip), acepromazine (2 mg/kg, ip) and xylazine (13 mg/kg, ip)(Henry Schein Inc., Melville, NY). Once deep sedation was achieved, a tracheostomy was performed and a PE-10 cannula was inserted in the trachea and stabilized with silk ligature. Control animals were immediately sacrificied with a supra-physiological dose of ketamine (300 mg/kg, ip). For ventilated mice, the cannula was connected to a custom built Voltek rodent ventilator (Voltek Enterprises, Toronto, CA). We ventilated mice for 8 hours using 2cmH2O positive end expiratory pressure (PEEP), inflating the lungs every hour to 20 cmH2O pressure as we have previously described. (16). The chest muscle was paralyzed with the injection of pancurorium (1mg/kg, ip)(Sigma-Aldrich) in ventilated mice to avoid spontaneous breathing. Heart rate and respiratory rate was continuously monitored and additional anesthesia was provided if a >15% increase in these parameters was detected. The animal protocol was approved by the BWH Institutional Animal Care and Use Committee (protocol #04477). Ventilated animals At the end of the each experiment, the animals were sacrificed with a supra-physiological dose of ketamine (300 mg/kg, ip). Subsequently, the chest cavity was opened, and the right lung was isolated and ligated at the main bronchus.Lungs were harvested and snap frozen in liquid nitrogen for total RNA extraction. Total RNA was extracted from lungs of controls (n=3) and mice submitted to ventilation (n=5) and there gene expression profiles were compared.

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Phosphoproteome profiling provides insight into the mechanisms of ventilator-induced lung injury.

Publications

Phosphoproteome profiling provides insight into the mechanisms of ventilator-induced lung injury.

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