Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: A better knowledge of the mechanisms and biomarkers of skin and lung damage in systemic sclerosis (SSc) related fibrosis remain a challenge. Our aim was to characterize serological and vascular manifestations, functional and histopathological features of skin and lung in the purpose of establishing a novel SSc murine model induced by Collagen V immunization.
Methods: Female C57BL/6 mice (n=19, IMU-COLV) were subcutaneously immunized with two doses of Col V (150μg) emulsified in complete Freund adjuvant, followed by two intramuscular boosters. The control group (n=19) did not receive Col V. After 120 days, respiratory mechanics, serum autoantibodies and vascular manifestations were examined. The skin and lung inflammatory process and the collagen gene/protein expression were analyzed.
Results: After immunization, the skin of the animals presented increased thickness (28.59±1.79 vs. 22.84±0.82; p=0.0132), epidermal rectification, decreased papillary dermis, and appendages atrophy, also showing increased deposition of collagen III (20.05±2.20 vs. 11.65±1.29; p=0.0147) and collagen V (3.65±0.47 vs. 1.05±0.18; p=0.011) fibers, and increased gene expression of COL5A1 (3,15±0,80 vs. 0,90±0,32; p=0,0316) and COL5A2 (2,10±0,24 vs. 0,56±0,24; p=0,0401). Vascular changes included endothelial cell activity and apoptosis by increased expression of VEGF (21.1±1.55 vs. 6.88±0.19; p< 0,004), endothelin-1 (10.20±0.81 vs. 2.35±0.44, p< 0,0022) and caspase-3 (21.21±1.34 vs. 8.26±0.29, p=0,0007), coinciding with increased gene expression of endothelin-1 (2,02±0,32 vs. 0,78±0,07; p=0,0351), VEGF (2.26±0.37 vs. 0.97±0.11; p=0.0019) and caspase-3 (1.99±0.17 vs. 0.92±0.10; p< 001). Immunized animals presented lung dysfunction characterized by increased tissue elastance and remodeling of parenchyma by non-specific interstitial pneumonia and vascular sclerosis. Compared to controls, immunization promoted increase of total collagen (6.95±0.42 vs. 5.33±0.31, p=0,0071), collagen I (25.90±3.31 vs. 5.57±0.59; p=0.003) and V (18.53±1.05 vs. 7.53±0.41; p< 0.0001) fibers in lung parenchyma, coinciding with COL1A1 (2.34±0.40 vs. 0.85±0.12; p=0.0070), COL1A2 (2.39±0.23 vs. 1.30±0.06; p=0.0016), COL5A1 (1.80±0.32 vs. 0.97±0.13; p=0.0379) and COL5A2 (1.56±0.18 vs. 0.93±0.10; p=0.014) gene expression. Anti-collagen III (0,15±0,006 vs. 0,09±0,005; p=0,0001) and IV (1,369±0,005 vs. 0,15±0,044; p< 0,0001) and antinuclear antibodies (ANA) (p=0,001) were detected in sera from IMU-COLV.
Conclusion: We demonstrated that cutaneous, vascular and pulmonary remodeling are mimicked by type V collagen-induced SSc mice model, thus representing a suitable preclinical model to study the mechanisms and therapeutic approaches in SSc.
To cite this abstract in AMA style:Teodoro W, Velosa A, Queiroz Z, Araujo L, Catanozi S, dos Santos Filho A, Bueno C, Vendramini M, Fernezlian S, Eher E, Tomaz de Miranda J, Lopes F, Pasoto S, Sampaio-Barros P, Capelozzi V. Proposition of a Novel Animal Model of Systemic Sclerosis Induced by Type V Collagen in C57BL/6 Mice Reproducing Fibrosis, Vasculopathy and Autoimmunity [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/proposition-of-a-novel-animal-model-of-systemic-sclerosis-induced-by-type-v-collagen-in-c57bl-6-mice-reproducing-fibrosis-vasculopathy-and-autoimmunity/. Accessed May 17, 2022.
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