title: TGF-beta signaling and collagen deposition in chronic rhinosinusitis.
abstract: BACKGROUND
  Chronic rhinosinusitis is an inflammatory disease with distinct cytokine and remodeling patterns.
  
  
  OBJECTIVE
  The objective was to analyze the presence of TGF-beta isoforms, receptors, intracellular signaling, and collagen deposition in chronic rhinosinusitis.
  
  
  METHODS
  Sinonasal mucosal samples obtained from chronic rhinosinusitis with nasal polyps (CRSwNP; n = 13), chronic rhinosinusitis without nasal polyps (CRSsNP; n = 13), and controls (n = 10) were analyzed for TGF-beta isoforms 1 and 2 by means of ELISA and IHC, and for TGF-beta R1, 2, and 3 by RT-PCR and IHC. As downstream proteins, phospho-Smad 2 (pSmad 2) and collagen were analyzed by performing immunostaining and picrosirius red staining, respectively.
  
  
  RESULTS
  TGF-beta 1 and 2 protein concentrations, TGF-beta receptor (R) I and TGF-beta RIII mRNA expression, the number of pSmad 2-positive cells, and total collagen amount were significantly higher in CRSsNP versus controls. In CRSwNP, TGF-beta 1 protein concentration, TGF-beta RII and TGF-beta RIII mRNA expression, the number of pSmad 2-positive cells, and total collagen amount were significantly lower versus controls. Only TGF-beta 2 protein was found higher in CRSwNP versus controls.
  
  
  CONCLUSIONS
  A high TGF-beta 1 protein expression, increased TGF-beta RI expression, and a high number of pSmad 2-positive cells all indicate an enhanced TGF-beta signaling in CRSsNP, whereas a low TGF-beta 1 protein concentration, a decreased expression of TGF-beta RII, and a low number of pSmad 2-positive cells in CRSwNP indicate a low level of TGF-beta signaling in CRSwNP. These findings are compatible with the remodeling patterns observed, reflected by a lack of collagen in CRSwNP, and excessive collagen production with thickening of the collagen fibers in the extracellular matrix in CRSsNP.
authors.affiliation: Upper Airway Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent University, Ghent, Belgium. Nicholas.Vanbruaene@Ugent.be
authors.forename: Nicholas
authors.initials: N
authors.lastname: Van Bruaene
authors.forename: Lara
authors.initials: L
authors.lastname: Derycke
authors.forename: Claudina Angela
authors.initials: CA
authors.lastname: Perez-Novo
authors.forename: Philippe
authors.initials: P
authors.lastname: Gevaert
authors.forename: Gabriele
authors.initials: G
authors.lastname: Holtappels
authors.forename: Natalie
authors.initials: N
authors.lastname: De Ruyck
authors.forename: Claude
authors.initials: C
authors.lastname: Cuvelier
authors.forename: Paul
authors.initials: P
authors.lastname: Van Cauwenberge
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012220:Rhinitis / Q000276:immunology*; D015398:Signal Transduction; D012852:Sinusitis / Q000276:immunology*; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D003094:Collagen