Tissue remodeling gene expression in a murine model of chronic rhinosinusitis

Nathan Sautter, Katherine L. Delaney, Frances A. Hausman, Dennis Trune

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective/Hypothesis: The matrix metalloproteinase (MMP), fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) families regulate tissue remodeling in many normal and pathophysiologic processes. We hypothesize that induction of chronic sinonasal inflammation will be associated with changes in regulation of these tissue remodeling cytokines. Methods: Balb/c mice aged 8 to 12 weeks were sensitized and treated with intranasal Aspergillus fumigatis (AF) three times per week for 1 week, 3 weeks, 2 months, and 3 months (n = 8 each time point). Sinonasal tissues were evaluated for changes in MMP, FGF, and BMP regulation using standard RT-PCR techniques. Additional snouts were processed for histology and immunohistochemistry. Untreated mouse snouts of identical age were used as controls. Results: Significant upregulation of MMP8 was observed at 2 months, and MMP1a, MMP7, MMP8, and MMP12 were all significantly upregulated at 3 months. FGF3 was significantly upregulated at 3 weeks and 3 months, and FGF5, FGF6, and FGF8 were all significantly upregulated at 3 months. BMP8b and BMP9 were significantly upregulated at 3 months. Histologic analysis revealed mucosal, stromal, and mucin gland hypertrophy, increased mucin production, and metaplasia with loss of cilia. Antibody staining was strongly positive in the AF-treated group. Conclusions: Induction of CRS is associated with time-dependent changes in tissue remodeling cytokine expression occurring in conjuction with inflammatory tissue changes. Antibody staining for upregulated cytokines suggests local production within the sinonasal mucosa. Further study is required to better understand the association between BMP, FGF, and MMP regulation and tissue remodeling changes resulting from chronic inflammation.

Original languageEnglish (US)
Pages (from-to)711-717
Number of pages7
JournalLaryngoscope
Volume122
Issue number4
DOIs
StatePublished - Apr 2012

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Gene Expression
Bone Morphogenetic Proteins
Fibroblast Growth Factors
Matrix Metalloproteinases
Mucins
Aspergillus
Cytokines
Staining and Labeling
Inflammation
Antibodies
Cilia
Metaplasia
Hypertrophy
Histology
Mucous Membrane
Up-Regulation
Immunohistochemistry
Polymerase Chain Reaction

Keywords

  • BMP
  • chronic rhinosinusitis
  • FGF
  • MMP
  • murine model
  • Tissue remodeling

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Tissue remodeling gene expression in a murine model of chronic rhinosinusitis. / Sautter, Nathan; Delaney, Katherine L.; Hausman, Frances A.; Trune, Dennis.

In: Laryngoscope, Vol. 122, No. 4, 04.2012, p. 711-717.

Research output: Contribution to journalArticle

Sautter, Nathan ; Delaney, Katherine L. ; Hausman, Frances A. ; Trune, Dennis. / Tissue remodeling gene expression in a murine model of chronic rhinosinusitis. In: Laryngoscope. 2012 ; Vol. 122, No. 4. pp. 711-717.
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