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CHARACTERIZATION OF CELLULAR AND MOLECULAR MECHANISM IN PRE-CLINICAL MODELS OF SCLERODERMA INDUCED BY COLLAGEN V

Abstract

Systemic sclerosis (ES) is a chronic connective tissue disease characterized by fibrosis of the skin and internal organs, activation of the immune system and proliferative vasculopathy, with a high mortality rate and low efficacy in the use of drugs, an extremely disabling and serious illness. Vasculopathy is an important feature in the pathogenesis of ES, due to the activation of endothelial cells, alteration of vascular tone and thickening of the intima layer, leading to vascular occlusion. The lesion promotes the release of growth factors, cytokines, chemokines and vasoactive mediators, resulting in increased vessel permeability and inflammatory cell chemotaxis, the presence of autoantibodies and proliferation of activated fibroblasts developing fibrosis due to the excessive production of collagen, mainly types I and III. In recent years, changes in the molecule of collagen V in several diseases have been described and our ES model was developed by immunization with Col V in healthy rabbits. It has recently been described that IL-17 can also stimulate the production of collagen V in the more severe forms of the disease. Therefore, considering the increased synthesis of Col V in the initial stages of ES, participation in the fibrillogenesis of Col I and III and relation of its increase with the activity of the disease, the objective of this project will be to clarify the action of Col V in cell signaling in human fibroblasts from normal human skin and its relation with TGF² and IL-17, trying to establish models "in vitro" and "in vivo" to study the mechanisms linked to the pathogenesis and to develop new therapeutic strategies for the control of this disease. (AU)

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VEICULO: TITULO (DATA)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TEODORO, WALCY ROSOLIA; DE JESUS QUEIROZ, ZELITA APARECIDA; DOS SANTOS, LAIS ARAUJO; CATANOZI, SERGIO; DOS SANTOS FILHO, ANTONIO; BUENO, CLEONICE; VENDRAMINI, MARGARETE B. G.; FERNEZLIAN, SANDRA DE MORAIS; EHER, ESMERALDA M.; SAMPAIO-BARROS, PERCIVAL D.; PASOTO, SANDRA GOFINET; LOPES, FERNANDA DEGOBBI T. Q. S.; PEREIRA VELOSA, ANA PAULA; CAPELOZZI, VERA LUIZA. Proposition of a novel animal model of systemic sclerosis induced by type V collagen in C57BL/6 mice that reproduces fibrosis, vasculopathy and autoimmunity. ARTHRITIS RESEARCH & THERAPY, v. 21, n. 1 DEC 1 2019. Web of Science Citations: 0.

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