Grant number: | 18/00415-0 |
Support Opportunities: | Regular Research Grants |
Start date: | December 01, 2018 |
End date: | November 30, 2021 |
Field of knowledge: | Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology |
Principal Investigator: | Walcy Paganelli Rosolia Teodoro |
Grantee: | Walcy Paganelli Rosolia Teodoro |
Host Institution: | Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Associated researchers: | Ana Paula Pereira Velosa ; Claudia Goldenstein Schainberg ; Sergio Catanozi ; Solange Carrasco ; Vera Luiza Capelozzi |
Associated scholarship(s): | 18/24210-8 - Evaluation of extracellular matrix proteins and endothelium activators in C57BL / 6 immunized pulmonary tissues with Col V, BP.TT |
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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