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Published on: June 28, 2018
Mechanical ventilation augments bleomycin-induced epithelial-mesenchymal transition through the Src pathway
Li-Fu Li1, Yung-Yang Liu2, Kuo-Chin Kao1
11] Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan [2] Department of Respiratory Therapy, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
High-tidal volume mechanical ventilation exacerbates lung injury and inflammation by promoting epithelial-mesenchymal transition (EMT) via the Src pathway. Inhibiting Src activity reduces this ventilator-induced lung damage.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Biomedical Engineering
Background:
- Mechanical ventilation in acute respiratory distress syndrome (ARDS) can cause lung damage, characterized by inflammation and fibrosis.
- The protein Src is implicated in pathways leading to fibrosis, including the production of PAI-1 and TGF-β1, and epithelial-mesenchymal transition (EMT).
- The precise mechanisms linking mechanical ventilation to EMT in ARDS remain incompletely understood.
Purpose of the Study:
- To investigate the hypothesis that high-tidal volume mechanical stretch augments lung inflammation and induces EMT through the Src signaling pathway.
- To elucidate the role of Src in ventilator-induced lung injury (VILI) and EMT.
Main Methods:
- Male C57BL/6 mice received bleomycin to induce acute lung injury (ALI).
- Mice were subjected to low or high tidal volume (VT) mechanical ventilation or served as controls.
- Wild-type and Src-deficient mice were used, along with pharmacological inhibition of Src (PP2).
Main Results:
- High-VT ventilation increased microvascular permeability, fibrotic markers (PAI-1, TGF-β1, collagen), fibroblast accumulation, and epithelial apoptosis in wild-type mice.
- High-VT ventilation decreased epithelial marker Zonula occludens-1 staining.
- These effects were significantly attenuated in Src-deficient mice and following Src inhibition with PP2.
Conclusions:
- High-tidal volume mechanical ventilation exacerbates lung injury and promotes EMT in a model of ALI.
- The Src pathway plays a crucial role in mediating ventilator-induced EMT and lung inflammation.
- Targeting the Src pathway may offer a therapeutic strategy to mitigate VILI.
