| First Author | Li LF | Year | 2014 |
| Journal | Lab Invest | Volume | 94 |
| Issue | 9 | Pages | 1017-29 |
| PubMed ID | 24955896 | Mgi Jnum | J:214246 |
| Mgi Id | MGI:5588618 | Doi | 10.1038/labinvest.2014.75 |
| Citation | Li LF, et al. (2014) Mechanical ventilation augments bleomycin-induced epithelial-mesenchymal transition through the Src pathway. Lab Invest 94(9):1017-29 |
| abstractText | Mechanical ventilation used in patients with acute respiratory distress syndrome (ARDS) can damage pulmonary epithelial cells by producing inflammatory cytokines and depositing excess collagen. Src participates in plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-beta1(TGF-beta1) production during the fibroproliferative phase of ARDS, which involves a process of epithelial-mesenchymal transition (EMT). The mechanisms regulating interactions between mechanical ventilation and EMT are unclear. We hypothesized that EMT induced by high-tidal volume (VT) mechanical stretch-augmented lung inflammation occurs through upregulation of the Src pathway. Five days after administering bleomycin to simulate acute lung injury (ALI), male C57BL/6 mice, either wild-type or Src-deficient, aged 3 months, weighing between 25 and 30 g, were exposed to low-VT (6 ml/kg) or high-VT (30 ml/kg) mechanical ventilation with room air for 1-5 h. Nonventilated mice were used as control subjects. We observed that high-VT mechanical ventilation increased microvascular permeability, PAI-1 and TGF-beta1 protein levels, Masson's trichrome staining, extracellular collagen levels, collagen gene expression, fibroblast accumulation, positive staining of alpha-smooth muscle actin and type I collagen, activation of Src signaling and epithelial apoptotic cell death in wild-type mice (P<0.05). Decreased staining of the epithelial marker, Zonula occludents-1, was also observed. Mechanical stretch-augmented EMT and epithelial apoptosis were attenuated in Src-deficient mice and pharmacological inhibition of Src activity by PP2 (P<0.05). Our data suggest that high-VT mechanical ventilation-augmented EMT after bleomycin-induced ALI partially depends on the Src pathway. |
