title: Lumican expression in diaphragm induced by mechanical ventilation.
abstract: 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)-β1. Lumican is known to participate in TGF-β1 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-β1 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 α-smooth muscle actin (α-SMA) mRNA, production of free radical and TGF-β1 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 α-SMA mRNA, and production of free radical and TGF-β1 protein. No significant diaphragmatic injury was found in mice subjected to normal tidal volume mechanical ventilation.
  
  
  CONCLUSIONS
  Our data showed that high tidal volume mechanical ventilation induced TGF-β1 production, TGF-β1-inducible genes, e.g., collagen, and diaphragmatic dysfunction through activation of the lumican.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Li-Fu
authors.initials: LF
authors.lastname: Li
authors.forename: Bao-Xiang
authors.initials: BX
authors.lastname: Chen
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
authors.forename: Winston W-Y
authors.initials: WW
authors.lastname: Kao
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
authors.forename: Pao-Hsien
authors.initials: PH
authors.lastname: Chu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D003964:Diaphragm / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation; D007632:Keratan Sulfate / Q000378:metabolism*; D000071234:Lumican; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011347:Procollagen / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D013990:Tidal Volume / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D011508:Chondroitin Sulfate Proteoglycans; D005353:Fibronectins; C000604307:Lum protein, mouse; D000071234:Lumican; D011347:Procollagen; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D003094:Collagen; D007632:Keratan Sulfate