title: Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.
abstract: BACKGROUND
  Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS.
  
  
  METHODS
  Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of the proteoglycans versican, perlecan, biglycan, and decorin, with and without transforming growth factor (TGF)-β(1). Fibroblast migration and proliferation were also studied.
  
  
  RESULTS
  At 6 and 12 months after LTx, versican production was higher in fibroblasts from LTx patients (p < 0.01 p < 0.01) than from controls. Fibroblasts from patients who later developed BOS were more responsive to TGF-β(1)-induced synthesis of versican and biglycan than patients without signs of rejection (p < 0.05). Production of perlecan and decorin was negatively correlated with fibroblast proliferation in fibroblasts at 6 months after LTx. In a more detailed case study of 2 patients, one with and one without BOS, the altered proteoglycan profile was associated with impaired lung function.
  
  
  CONCLUSIONS
  LTx changes the phenotype of fibroblasts to a non-proliferative but extracellular matrix-producing cell due to wound healing involving TGF-β(1). If not controlled, this may lead to development of BOS.
authors.affiliation: Lung Biology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. Annika.Andersson_Sjoland@med.lu.se
authors.forename: Annika
authors.initials: A
authors.lastname: Andersson-Sjöland
authors.forename: Lena
authors.initials: L
authors.lastname: Thiman
authors.forename: Kristian
authors.initials: K
authors.lastname: Nihlberg
authors.forename: Oskar
authors.initials: O
authors.lastname: Hallgren
authors.forename: Sara
authors.initials: S
authors.lastname: Rolandsson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Skog
authors.forename: Lena
authors.initials: L
authors.lastname: Mared
authors.forename: Lennart
authors.initials: L
authors.lastname: Hansson
authors.forename: Leif
authors.initials: L
authors.lastname: Eriksson
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000473:pathology* / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism; D013577:Syndrome; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D011509:Proteoglycans; D053773:Transforming Growth Factor beta1