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J Allergy Clin Immunol. 2009 Aug;124(2):253-9, 259.e1-2. doi: 10.1016/j.jaci.2009.04.013. Epub 2009 Jun 4.

TGF-beta signaling and collagen deposition in chronic rhinosinusitis.

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1
Upper Airway Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent University, Ghent, Belgium. Nicholas.Vanbruaene@Ugent.be

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.

CONCLUSION:

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.

PMID:
19500825
DOI:
10.1016/j.jaci.2009.04.013
[Indexed for MEDLINE]
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