Tissue remodeling gene expression in a murine model of chronic rhinosinusitis

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 8–12 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. Conclusion 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.

Vitamin D3 as a novel regulator of basic fibroblast growth factor in chronic rhinosinusitis with nasal polyposis

“…The above studies, 24,26,27 along with our current investigation, appear to conflict with previous murine studies reported by Sautter et al, in which FGF-2 was down-regulated at one and three weeks in a murine model of CRS [28]. However, there are several limitations to direct comparison of the human and mouse experimental models.…”

Microarray analysis of the genes associated with osteitis in chronic rhinosinusitis

“…Its specific role in bone remodeling in CRS patients is not clear, whereas the BMP family was shown to play a role in tissue remodeling. Some members of the BMP family were shown to be reduced or increased in patients with chronic sinusitis in several studies . The consideration of GDF‐5 having a role in bone remodeling was enhanced by one of our study results, which showed that GDF‐5 was released more in osteitic bone tissue when compared to the mucosa in the experimental group (FC = 9.24).…”

Topical cathelicidin (LL‐37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model

“…28,29 Briefly, inflammation was assessed by light microscopic examination. The control and OE tissue were examined in a blinded fashion.…”