TGF-beta signaling and collagen deposition in chronic rhinosinusitis.
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.
Van Bruaene
Nicholas
N
Upper Airway Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent University, Ghent, Belgium. Nicholas.Vanbruaene@Ugent.be
Derycke
Lara
L
Perez-Novo
Claudina Angela
CA
Gevaert
Philippe
P
Holtappels
Gabriele
G
De Ruyck
Natalie
N
Cuvelier
Claude
C
Van Cauwenberge
Paul
P
Bachert
Claus
C
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
D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D003094:Collagen