| First Author | Li LF | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 9 | Pages | e24692 |
| PubMed ID | 21931815 | Mgi Jnum | J:177690 |
| Mgi Id | MGI:5295830 | Doi | 10.1371/journal.pone.0024692 |
| Citation | Li LF, et al. (2011) Lumican expression in diaphragm induced by mechanical ventilation. PLoS One 6(9):e24692 |
| abstractText | BACKGROUND: Diaphragmatic dysfunction found in the patients with acute lung injury required prolonged mechanical ventilation. Mechanical ventilation can induce production of inflammatory cytokines and excess deposition of extracellular matrix proteins via up-regulation of transforming growth factor (TGF)-beta1. Lumican is known to participate in TGF-beta1 signaling during wound healing. The mechanisms regulating interactions between mechanical ventilation and diaphragmatic injury are unclear. We hypothesized that diaphragmatic damage by short duration of mechanical stretch caused up-regulation of lumican that modulated TGF-beta1 signaling. METHODS: Male C57BL/6 mice, either wild-type or lumican-null, aged 3 months, weighing between 25 and 30 g, were exposed to normal tidal volume (10 ml/kg) or high tidal volume (30 ml/kg) mechanical ventilation with room air for 2 to 8 hours. Nonventilated mice served as control groups. RESULTS: High tidal volume mechanical ventilation induced interfibrillar disassembly of diaphragmatic collagen fiber, lumican activation, type I and III procollagen, fibronectin, and alpha-smooth muscle actin (alpha-SMA) mRNA, production of free radical and TGF-beta1 protein, and positive staining of lumican in diaphragmatic fiber. Mechanical ventilation of lumican deficient mice attenuated diaphragmatic injury, type I and III procollagen, fibronectin, and alpha-SMA mRNA, and production of free radical and TGF-beta1 protein. No significant diaphragmatic injury was found in mice subjected to normal tidal volume mechanical ventilation. CONCLUSION: Our data showed that high tidal volume mechanical ventilation induced TGF-beta1 production, TGF-beta1-inducible genes, e.g., collagen, and diaphragmatic dysfunction through activation of the lumican. |
