title: Molecular mechanisms of lung cell activation induced by cyclic stretch.
abstract: OBJECTIVE
  To review molecular mechanisms of lung cell activation by stretch.
  
  
  METHODS
  Published original and review articles.
  
  
  METHODS
  Positive-pressure mechanical ventilation is associated with both beneficial and harmful effects. Data indicate that mechanical ventilation can induce, or increase, lung inflammation. This effect is clearly linked to the degree of lung cell stretching. By modeling cyclic stretch in cultured cells, it has been possible to investigate the cellular pathways activated by this mechanical strain. Integrin receptors, proteins of the focal adhesion plaque, and the cytoskeleton itself participate in the multiple molecular complex that senses cyclic stretch, transforming a mechanical signal into a biological response. Several intracellular signaling pathways then are activated and eventually result in increased transcription of genes harboring "stretch-response elements" in their promoters. Among these pathways, the mitogen-activated protein kinase signaling cascade appears to be central in mediating the effects of cell stretching. Other posttranscriptional mechanisms, such as messenger RNA stabilization and the secretion of preformed mediators, also may account for the secretion of inflammatory mediators after cyclic stretch.
  
  
  CONCLUSIONS
  Identification of the relevant molecular mechanisms will help in the development of novel ventilatory and pharmacologic therapeutic strategies aimed at preventing the deleterious effects of mechanical ventilation.
authors.affiliation: Division of Medical Intensive Care, University Hospital, Geneva, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Pugin
mesh_terms: D000818:Animals; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology*
chemical_list: D020929:Mitogen-Activated Protein Kinase Kinases