Abstract
BackgroundThe purpose of this study was to evaluate collagen deposition, mRNA collagen synthesis and TGF-beta expression in the lung tissue in an experimental model of scleroderma after collagen V-induced nasal tolerance.MethodsFemale New Zealand rabbits (N = 12) were immunized with 1 mg/ml of collagen V in Freund's adjuvant (IM). After 150 days, six immunized animals were tolerated by nasal administration of collagen V (25 μg/day) (IM-TOL) daily for 60 days. The collagen content was determined by morphometry, and mRNA expressions of types I, III and V collagen were determined by Real-time PCR. The TGF-beta expression was evaluated by immunostaining and quantified by point counting methods. To statistic analysis ANOVA with Bonferroni test were employed for multiple comparison when appropriate and the level of significance was determined to be p < 0.05.ResultsIM-TOL, when compared to IM, showed significant reduction in total collagen content around the vessels (0.371 ± 0.118 vs. 0.874 ± 0.282, p < 0.001), bronchioles (0.294 ± 0.139 vs. 0.646 ± 0.172, p < 0.001) and in the septal interstitium (0.027 ± 0.014 vs. 0.067 ± 0.039, p = 0.026). The lung tissue of IM-TOL, when compared to IM, showed decreased immunostaining of types I, III and V collagen, reduced mRNA expression of types I (0.10 ± 0.07 vs. 1.0 ± 0.528, p = 0.002) and V (1.12 ± 0.42 vs. 4.74 ± 2.25, p = 0.009) collagen, in addition to decreased TGF-beta expression (p < 0.0001).ConclusionsCollagen V-induced nasal tolerance in the experimental model of SSc regulated the pulmonary remodeling process, inhibiting collagen deposition and collagen I and V mRNA synthesis. Additionally, it decreased TGF-beta expression, suggesting a promising therapeutic option for scleroderma treatment.
Highlights
The purpose of this study was to evaluate collagen deposition, mRNA collagen synthesis and Transforming growth factor (TGFbeta) expression in the lung tissue in an experimental model of scleroderma after collagen V-induced nasal tolerance
Considering that we have already demonstrated the efficacy of nasal tolerance with collagen V in skin remodeling of animals with Systemic Sclerosis (SSc) [18], in the present study we evaluated the amount of collagen deposition, mRNA collagen synthesis and TGF-beta expression in pulmonary septal and bronchovascular interstitium of rabbits after collagen V-induced nasal tolerance in experimental SSc
The density of the collagen fibers is decreased around the vessels (0.371 ± 0.118 vs. 0.874 ± 0.282; p < 0.001), bronchioles (0.294 ± 0.139 vs. 0.646 ± 0.172; p < 0.001) and in the septal interstitium (0.027 ± 0.014 vs. 0.067 ± 0.039, p = 0.026) in tolerated animals when compared to the immunized ones (Figure 2A, B and 2C)
Summary
The purpose of this study was to evaluate collagen deposition, mRNA collagen synthesis and TGFbeta expression in the lung tissue in an experimental model of scleroderma after collagen V-induced nasal tolerance. Progressive Systemic Sclerosis (SSc) is an autoimmune disease of unknown pathogenesis, characterized by the increased extracellular matrix (ECM) synthesis, vascular remodeling and autoantibody emergence, which results in scarring in multiple organs. Interstitial lung fibrosis, of variable intensity, affects approximately 90% of patients, and the frequency collagen synthesis and degradation and interfering with ECM remodeling. Collagen V is a highly conserved molecule among different animal species [4,5] and is normally found in lung ECM, composing the heterotypic fibrils with types I and III collagen. Collagen V is a minor collagen fraction not normally exposed in the tissues [7,8,9,10], retaining the amino- and carboxy-terminals, making it quite immunogenic
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