Role of FIZZ1/RELMa in experimental silicosis

• Grant number: 16/21429-3
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2017
• Effective date (End): February 28, 2019
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Vera Luiza Capelozzi
• Grantee: Vanessa Martins da Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Instillation of silica instillation in mice results in pathological changes that mimic the pattern of human silicosis, an occupational lung disease characterized by restrictive airway obstruction, inflammation and fibrosis. FIZZ1 belongs to the class of secreted proteins and is highly expressed in the lung parenchyma by alveolar epithelial cells. It is directly involved in the differentiation of myofibroblasts by IL-4 and IL-13-dependent STAT6 STAT6 signaling pathway in pulmonary fibrotic process induced by bleomycin. Since FIZZ1 has direct action on myofibroblasts and is involved in the fibrotic process, it is intended, in this project, to study the role of this molecule and their signaling pathway in fibrogenic mechanisms of silicosis. FIZZ1 +/+ and FIZZ1 -/- animal groups will receive by intrataqueal instillation, silica particles or saline. The expression of FIZZ1, ±-SMA and Notch1 in the lung parenchyma of silicosis and healthy animals will be evaluated and quantified by Western blot, RT-PCR and immunohistochemistry. The degree of silica-induced lung injury in both groups will be determined by optical and electron microscopy, hydroxyproline concentration and Western Blot. We expect elucidate the role of FIZZ1 signaling pathway involved in the pathological changes caused by the inhalation of silica particles, and eventually use it as sensitive biomarker of disease and potential therapeutic target in the future. (AU)

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)

MARTINS, VANESSA; DA SILVA, ADRIANA LOPES; TEODORO, WALCY ROSOLIA; PEREIRA VELOSA, ANA PAULA; BALANCIN, MARCELO LUIZ; CRUZ, FERNANDA FERREIRA; SILVA, PEDRO LEME; MACEDO ROCCO, PATRICIA RIEKEN; CAPELOZZI, VERA LUIZA. In situ evidence of collagen V and signaling pathway of found inflammatory zone 1 (FIZZ1) is associated with silicotic granuloma in lung mice. PATHOLOGY RESEARCH AND PRACTICE, v. 216, n. 9, SEP 2020. (16/21429-3, 18/20403-6)