title: Increased pulmonary Wnt (wingless/integrated)-signaling in patients with sarcoidosis.
abstract: BACKGROUND
  Sarcoidosis is an inflammatory multisystemic granulomatous disease of unknown aetiology commonly affecting the lungs, and pulmonary fibrosis often develops in chronic sarcoidosis. It has been suggested that Wnt (Wingless/integrated)-signaling has a role in inflammatory and fibrotic processes in the lungs, but its role in sarcoidosis has not been investigated. We hypothesised that Wnts secreted from T cells or other inflammatory cells have a role in the pathogenesis of sarcoidosis.
  
  
  METHODS
  Brush biopsies and bronchoalveolar lavage (BAL) were obtained through bronchoscopy from healthy controls (n = 18) and patients with sarcoidosis (n = 48). Semi-quantitative RT-PCR, electrophoretic mobility shift assay (EMSA) and immunocytochemistry were performed to analyse Wnt expression and activation of the Wnt-signal transducer β-catenin.
  
  
  RESULTS
  Altered expression of Wnt5A, Wnt7A and Wnt7B mRNA in BAL cells was observed, as well as an increased activation of β-catenin, measured by EMSA and confirmed with immunocytochemistry, in resident lung cells from patients with sarcoidosis. More pronounced changes in Wnt expression were seen with advancing disease stage. Thus, by three independent methods, we have found evidence of increased pulmonary Wnt-activation in sarcoidosis.
  
  
  CONCLUSIONS
  In the lungs of patients with sarcoidosis there is a previously unappreciated increased Wnt-signal activation that could contribute to the inflammatory processes.
authors.affiliation: Department of Medicine Solna, Respiratory Medicine Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. bettina.levanen@ki.se
authors.forename: Bettina
authors.initials: B
authors.lastname: Levänen
authors.forename: Asa M
authors.initials: AM
authors.lastname: Wheelock
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
authors.forename: Magnus
authors.initials: M
authors.lastname: Nord
mesh_terms: D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017565:Sarcoidosis, Pulmonary / Q000235:genetics / Q000378:metabolism*; D051155:Wnt1 Protein / Q000378:metabolism*
chemical_list: D051155:Wnt1 Protein