title: Lung fibroblasts share mesenchymal stem cell features which are altered in chronic obstructive pulmonary disease via the overactivation of the Hedgehog signaling pathway.
abstract: BACKGROUND
  Alteration of functional regenerative properties of parenchymal lung fibroblasts is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD). However, what these functions are and how they are impaired in COPD remain poorly understood. Apart from the role of fibroblasts in producing extracellular matrix, recent studies in organs different from the lung suggest that such cells might contribute to repair processes by acting like mesenchymal stem cells. In addition, several reports sustain that the Hedgehog pathway is altered in COPD patients thus aggravating the disease. Nevertheless, whether this pathway is dysregulated in COPD fibroblasts remains unknown.
  
  
  OBJECTIVE
  We investigated the stem cell features and the expression of Hedgehog components in human lung fibroblasts isolated from histologically-normal parenchymal tissue from 25 patients--8 non-smokers/non-COPD, 8 smokers-non COPD and 9 smokers with COPD--who were undergoing surgery for lung tumor resection.
  
  
  RESULTS
  We found that lung fibroblasts resemble mesenchymal stem cells in terms of cell surface marker expression, differentiation ability and immunosuppressive potential and that these properties were altered in lung fibroblasts from smokers and even more in COPD patients. Furthermore, we showed that some of these phenotypic changes can be explained by an over activation of the Hedgehog signaling in smoker and COPD fibroblasts.
  
  
  CONCLUSIONS
  Our study reveals that lung fibroblasts possess mesenchymal stem cell-features which are impaired in COPD via the contribution of an abnormal Hedgehog signaling. These processes should constitute a novel pathomechanism accounting for disease occurrence and progression.
authors: Inserm, U955, Equipe 12, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France.
authors: Florence
authors: F
authors: Figeac
authors: Inserm, U955, Equipe 4, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France.
authors: Maylis
authors: M
authors: Dagouassat
authors: Inserm, U955, Equipe 12, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France.
authors: Meriem
authors: M
authors: Mahrouf-Yorgov
authors: Inserm, U955, Equipe 4, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France; AP-HP, Hôpital Henri Mondor- A. Chenevier, Département d'Hématologie et Immunologie Biologiques, Créteil, 94000, France.
authors: Sabine
authors: S
authors: Le Gouvello
authors: Inserm, U955, Equipe 12, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France.
authors: Céline
authors: C
authors: Trébeau
authors: Inserm, U955, Equipe 12, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France.
authors: Angeliqua
authors: A
authors: Sayed
authors: Institut Mutualiste Montsouris, Département thoracique, Paris, France.
authors: Jean-Baptiste
authors: JB
authors: Stern
authors: Institut Mutualiste Montsouris, Département anatomopathologie, Paris, France.
authors: Pierre
authors: P
authors: Validire
authors: Université Paris Est, Faculté de Médecine, Créteil, 94000, France; AP-HP, Hôpital Henri Mondor-A. Chenevier, Service de Physiologie Explorations Fonctionnelles, Créteil, 94000, France; Inserm, U955, Equipe 3, Créteil, 94000, France.
authors: Jean-Luc
authors: JL
authors: Dubois-Randé
authors: Inserm, U955, Equipe 4, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France; Hôpital Intercommunal de Créteil, Service de pneumologie et pathologie professionnelle, Créteil, 94000, France.
authors: Jorge
authors: J
authors: Boczkowski
authors: Institut de Pharmacologie Moléculaire et Cellulaire CNRS, Valbonne 06560, France; Université de Nice-Sophia-Antipolis, Nice 06108, France.
authors: Isabelle
authors: I
authors: Mus-Veteau
authors: Inserm, U955, Equipe 12, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France.
authors: Anne-Marie
authors: AM
authors: Rodriguez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000601:surgery*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects
chemical_list: D053823:Hedgehog Proteins