title: Gelsolin expression is necessary for the development of modelled pulmonary inflammation and fibrosis.
abstract: BACKGROUND
  Despite intense research efforts, the aetiology and pathogenesis of idiopathic pulmonary fibrosis remain poorly understood. Gelsolin, an actin-binding protein that modulates cytoskeletal dynamics, was recently highlighted as a likely disease modifier through comparative expression profiling and target prioritisation.
  
  
  METHODS
  To decipher the possible role of gelsolin in pulmonary inflammation and fibrosis, immunocytochemistry on tissue microarrays of human patient samples was performed followed by computerised image analysis. The results were validated in the bleomycin-induced animal model of pulmonary inflammation and fibrosis using genetically-modified mice lacking gelsolin expression. Moreover, to gain mechanistic insights into the mode of gelsolin activity, a series of biochemical analyses was performed ex vivo in mouse embryonic fibroblasts.
  
  
  RESULTS
  Increased gelsolin expression was detected in lung samples of patients with idiopathic interstitial pneumonia as well as in modelled pulmonary inflammation and fibrosis. Genetic ablation of gelsolin protected mice from the development of modelled pulmonary inflammation and fibrosis attributed to attenuated epithelial apoptosis.
  
  
  CONCLUSIONS
  Gelsolin expression is necessary for the development of modelled pulmonary inflammation and fibrosis, while the caspase-3-mediated gelsolin fragmentation was shown to be an apoptotic effector mechanism in disease pathogenesis and a marker of lung injury.
authors.affiliation: Dr VInstitute of Immunology, Alexander Fleming Biomedical Sciences Research Center, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Oikonomou
authors.forename: A
authors.initials: A
authors.lastname: Thanasopoulou
authors.forename: A
authors.initials: A
authors.lastname: Tzouvelekis
authors.forename: V
authors.initials: V
authors.lastname: Harokopos
authors.forename: T
authors.initials: T
authors.lastname: Paparountas
authors.forename: I
authors.initials: I
authors.lastname: Nikitopoulou
authors.forename: W
authors.initials: W
authors.lastname: Witke
authors.forename: A
authors.initials: A
authors.lastname: Karameris
authors.forename: A
authors.initials: A
authors.lastname: Kotanidou
authors.forename: D
authors.initials: D
authors.lastname: Bouros
authors.forename: V
authors.initials: V
authors.lastname: Aidinis
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D001761:Bleomycin; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D018260:Gelsolin / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D020556:Neutrophil Infiltration; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D020545:Respiratory Mucosa / Q000473:pathology
chemical_list: D018260:Gelsolin; D001761:Bleomycin