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Abstract Number: 1040

Proposition of a Novel Animal Model of Systemic Sclerosis Induced by Type V Collagen in C57BL/6 Mice Reproducing Fibrosis, Vasculopathy and Autoimmunity

Walcy Teodoro1, Ana Paula Velosa 2, Zelita Aparecida Queiroz 1, Lais Araujo 3, Sergio Catanozi 1, Antonio dos Santos Filho 4, Cleonice Bueno 4, Margarete Vendramini 4, Sandra Moraes Fernezlian 1, Esmeralda Eher 4, Jurandir Tomaz de Miranda 1, Fernanda Lopes 4, Sandra G. Pasoto 5, Percival Degrava Sampaio-Barros 6 and Vera Luiza Capelozzi 1, 1Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR, Sao Paulo, Sao Paulo, Brazil, 2Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR, São Paulo, Sao Paulo, Brazil, 3Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR, São Paulo, Sao Paulo, Brazil, 4Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR, Sao Paulo, Sao Paulo, Brazil, 5Rheumatology Division, Hospital das Clinicas, Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil., Sao Paulo, Brazil, 6Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR, Brazil, Sao Paulo, Brazil

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Animal models, Collagen, fibrosis and vasculopaty, Systemic sclerosis

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Session Information

Date: Monday, November 11, 2019

Session Title: Systemic Sclerosis & Related Disorders – Basic Science Poster

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.


Disclosure: W. Teodoro, None; A. Velosa, None; Z. Queiroz, None; L. Araujo, None; S. Catanozi, None; A. dos Santos Filho, None; C. Bueno, None; M. Vendramini, None; S. Fernezlian, None; E. Eher, None; J. Tomaz de Miranda, None; F. Lopes, None; S. Pasoto, Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP #2015/03756-4), 2; P. Sampaio-Barros, None; V. Capelozzi, None.

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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