TGF-beta signaling and collagen deposition in chronic rhinosinusitis

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chronic Disease
  • Collagen / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nasal Polyps / immunology*
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Rhinitis / immunology*
  • Signal Transduction
  • Sinusitis / immunology*
  • Smad2 Protein / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Young Adult

Substances

  • Receptors, Transforming Growth Factor beta
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta
  • Collagen