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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Proposition of a novel animal model of systemic sclerosis induced by type V collagen in C57BL/6 mice that reproduces fibrosis, vasculopathy and autoimmunity

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Teodoro, Walcy Rosolia [1] ; de Jesus Queiroz, Zelita Aparecida [1] ; dos Santos, Lais Araujo [1] ; Catanozi, Sergio [2, 3] ; dos Santos Filho, Antonio [1] ; Bueno, Cleonice [1] ; Vendramini, Margarete B. G. [1] ; Fernezlian, Sandra de Morais [4] ; Eher, Esmeralda M. [4] ; Sampaio-Barros, Percival D. [1] ; Pasoto, Sandra Gofinet [1] ; Lopes, Fernanda Degobbi T. Q. S. [5] ; Pereira Velosa, Ana Paula [1] ; Capelozzi, Vera Luiza [4]
Total Authors: 14
Affiliation:
[1] Univ Sao Paulo, Fac Med, Rheumatol Div, Hosp Clin, Av Dr Arnaldo 455, Sala 3124, BR-01246903 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Med, Lipid Lab Endocrinol, Hosp Clin, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Fac Med, Metabol Discipline, Hosp Clin, Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Fac Med, Dept Pathol, Hosp Clin, Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Fac Med, Expt Therapy Lab, Dept Clin Med, Hosp Clin, Sao Paulo, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: ARTHRITIS RESEARCH & THERAPY; v. 21, n. 1 DEC 1 2019.
Web of Science Citations: 0
Abstract

Background: Type V collagen (Col V) has the potential to become an autoantigen and has been associated with the pathogenesis of systemic sclerosis (SSc). We characterized serological, functional, and histopathological features of the skin and lung in a novel SSc murine model induced by Col V immunization. Methods: Female C57BL/6 mice (n = 19, IMU-COLV) were subcutaneously immunized with two doses of Col V (125 mu g) emulsified in complete Freund adjuvant, followed by two intramuscular boosters. The control group (n = 19) did not receive Col V. After 120 days, we examined the respiratory mechanics, serum autoantibodies, and vascular manifestations of the mice. The skin and lung inflammatory processes and the collagen gene/protein expressions were analyzed. Results: Vascular manifestations were characterized by endothelial cell activity and apoptosis, as shown by the increased expression of VEGF, endothelin-1, and caspase-3 in endothelial cells. The IMU-COLV mice presented with increased tissue elastance and a nonspecific interstitial pneumonia (NSIP) histologic pattern in the lung, combined with the thickening of the small and medium intrapulmonary arteries, increased Col V fibers, and increased COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2 gene expression. The skin of the IMU-COLV mice showed thickness, epidermal rectification, decreased papillary dermis, atrophied appendages, and increased collagen, COL5A1, and COL5A2 gene expression. Anti-collagen III and IV and ANA antibodies were detected in the sera of the IMU-COLV mice. Conclusion: We demonstrated that cutaneous, vascular, and pulmonary remodeling are mimicked in the Col V-induced SSc mouse model, which thus represents a suitable preclinical model to study the mechanisms and therapeutic approaches for SSc. (AU)

FAPESP's process: 18/24210-8 - Evaluation of extracellular matrix proteins and endothelium activators in C57BL / 6 immunized pulmonary tissues with Col V
Grantee:Zelita Aparecida de Jesus Queiroz
Support type: Scholarships in Brazil - Technical Training Program - Technical Training
FAPESP's process: 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promise therapeutic targets
Grantee:Vera Luiza Capelozzi
Support type: Research Projects - Thematic Grants
FAPESP's process: 16/05617-4 - EVALUATION OF ANTIGENIC POTENTIAL OF THE COLLAGEN TYPE V IN SYSTEMIC SCLEROSIS
Grantee:Ana Paula Pereira Velosa
Support type: Regular Research Grants
FAPESP's process: 18/00415-0 - CHARACTERIZATION OF CELLULAR AND MOLECULAR MECHANISM IN PRE-CLINICAL MODELS OF SCLERODERMA INDUCED BY COLLAGEN V
Grantee:Walcy Paganelli Rosolia Teodoro
Support type: Regular Research Grants