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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: ARTHRITIS RESEARCH & THERAPY; v. 21, n. 1 DEC 1 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/24210-8 - Avaliação das proteínas da matriz extracelular e das ativadoras de endotélio no tecido pulmonar de camundongos C57BL/6 imunizados com Col V
• Beneficiário: Zelita Aparecida de Jesus Queiroz
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 18/20403-6 - Marcadores biomoleculares de proliferação e remodelamento em doenças respiratórias agudas e crônicas: promissores alvos terapêuticos
• Beneficiário: Vera Luiza Capelozzi
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/05617-4 - Avaliação do potencial antigênico do colágeno tipo v em esclerose sistêmica
• Beneficiário: Ana Paula Pereira Velosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/00415-0 - Caracterização do mecanismo celular e molecular em modelos pré-clínicos de esclerodermia induzidos pelo colágeno v
• Beneficiário: Walcy Paganelli Rosolia Teodoro
• Modalidade de apoio: Auxílio à Pesquisa - Regular