title: Tissue remodeling gene expression in a murine model of chronic rhinosinusitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Oregon Health Sciences University, Department of Otolaryngology-Head and Neck Surgery, Portland, Oregon 97239, USA. sauttern@ohsu.edu
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Sautter
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Delaney
authors.forename: Frances A
authors.initials: FA
authors.lastname: Hausman
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Trune
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000473:pathology; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000235:genetics*; D012220:Rhinitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012852:Sinusitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D019485:Bone Morphogenetic Proteins; D005346:Fibroblast Growth Factors; D012313:RNA; D020782:Matrix Metalloproteinases