PT  - JOURNAL ARTICLE
AU  - Li-Fu Li
AU  - Chung-Chi Huang
AU  - Kuo-Chin Kao
AU  - Chih-Hao Chang
AU  - Cheng-Yiu Hung
TI  - Src regulates ventilation-induced epithelial-mesenchymal transition and epithelial apoptosis
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - 3429
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/3429.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/3429.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Background and objective:Mechanical ventilation (MV) used in patients with acute lung injury (ALI) can damage pulmonary epithelial cells through production of inflammatory cytokines and excess deposition of collagen. Src participates in plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) production during the organic phase of ALI, which involves a process of epithelial-mesenchymal transition (EMT). The mechanisms regulating interactions between MV and EMT are unclear. We hypothesized that EMT and epithelial apoptosis induced by high-tidal-volume MV modulated PAI-1 and TGF-β1 through upregulating the Src pathway.Methods: Five days after administering bleomycin to simulate ALI, C57BL/6 mice, either wild-type or Src-deficient, were exposed to low-tidal-volume (6 ml/kg) or high-tidal-volume (30 ml/kg) MV with room air for 1 to 5 h. Nonventilated mice were used as control subjects.Results:We observed that high-tidal-volume MV increased microvascular permeability, PAI-1 and TGF-β1 production, Masson's trichrome staining, extracellular collagen levels, fibroblast accumulation, positive staining of α-smooth muscle actin and type I collagen, activation of Src signaling, and epithelial apoptotic cell death in wild-type mice. Decreased staining of the epithelial marker, Zonula occludents-1, was also observed. MV-augmented EMT and epithelial apoptosis were attenuated in Src-deficient mice and pharmacological inhibition with PP2.Conclusions: Our data suggest that high-tidal-volume MV-augmented pulmonary fibrosis and epithelial apoptosis after bleomycin-induced ALI depends, in part, on EMT regulated by the Src pathway.Grant:NSC101-2314-B-182A-088-MY3.