In situ evidence of collagen V and signaling pathway of found inflammatory zone 1 (FIZZ1) is associated with silicotic granuloma in lung mice

Author(s)

Martins, Vanessa ^[1] ; da Silva, Adriana Lopes ^[2] ; Teodoro, Walcy Rosolia ^[3] ; Pereira Velosa, Ana Paula ^[3] ; Balancin, Marcelo Luiz ^[1] ; Cruz, Fernanda Ferreira ^[2] ; Silva, Pedro Leme ^[2] ; Macedo Rocco, Patricia Rieken ^[2] ; Capelozzi, Vera Luiza ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Pathol, Fac Med, Av Dr Arnaldo 455, Room 1143, Sao Paulo - Brazil

^[2] Univ Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, Lab Pulm Invest, Rio De Janeiro - Brazil

^[3] Univ Sao Paulo, Rheumatol Discipline, Fac Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: PATHOLOGY RESEARCH AND PRACTICE; v. 216, n. 9 SEP 2020.
• Web of Science Citations: 0

Abstract

Inhalation of silica particles causes silicosis: an occupational lung disease characterized by persistent inflammation with granuloma formation that leads to tissue remodeling and impairment of lung function. Although silicosis has been studied intensely, little is known about the crucial cellular mechanisms that initiate and drive the process of inflammation and fibrosis. Recently, found in inflammatory zone 1 (FIZZ1) protein, produced by alveolar macrophages and fibroblasts have been shown to induce the proliferation of myofibroblasts and their transdifferentiation, causing tissue fibrosis. Moreover, autoimmunogenic collagen V, produced by alveolar epithelial cells and fibroblasts, is involved in the pathophysiology of interstitial pulmonary fibrosis and bleomycin-induced lung fibrosis. Based on the aforementioned we hypothesized that FIZZ1 and collagen V may be involved in the silicotic granuloma process in mice lungs. Male C57BL/6 mice (N = 20) received intratracheal administration of silica particles (Silica; 20 mg in 50 mu L saline) or saline (Control; 50 mu L). After 15 days, the lung histology was performed through immunohistochemistry and morphometric analysis. Within silicotic granulomas, collagen V and FIZZ1 increased, while peroxisome proliferator-activated receptor gamma (PPAR gamma) positive cells decreased. In addition, the expression of proteins Notch-1, alpha smooth muscle actin (alpha-SMA) and macrophages163 (CD163) were higher in silicotic granulomas than control lungs. A significant positive correlation was found between collagen V and FIZZ1 (r = 0.70; p < 0.05), collagen V and Notch-1 (r = 0.72; p < 0.05), whereas Collagen V was inversely associated with peroxisome proliferator-activated receptor gamma (r=-0.69; p < 0.05). These findings suggested that collagen V association with FIZZ1, Notch-1 and PPAR gamma might be a key pathogenic mechanism for silicotic granulomas in mice lungs. (AU)

• FAPESP's process: 16/21429-3 - Role of FIZZ1/RELMa in experimental silicosis
• Grantee: Vanessa Martins da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets
• Grantee: Vera Luiza Capelozzi
• Support Opportunities: Research Projects - Thematic Grants