Effect of particulate matter (PM) on inflammatory, oxidative and proliferative pathways in cultured lung cells

• Grant number: 24/09623-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mirian Aparecida Boim
• Grantee: Giovanna de Sant'Ana
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Air pollution is one of the main environmental problems, significantly affecting public health, mainly causing respiratory diseases. Among the main pollutants is particulate matter (PM), which is considered one of the most harmful substances in atmospheric air. MP can be classified according to its size, with fine MP consisting of particles d 2.5 µm in diameter. Exposure to PM2.5 is associated with respiratory and cardiovascular diseases due to its ability to penetrate deep into the lungs, causing structural damage and impaired lung function. The molecular mechanisms of air pollution-induced lung toxicity are complex and not yet fully understood. Data suggest that there is a plausible relationship between cellular toxicity and activation of multiple biological processes, including inflammatory responses, oxidative stress, mitochondrial injury, apoptosis and epithelial-mesenchymal transition, with proliferative potential. This study aims to evaluate the effects of MP2.5 on lung epithelial cells, both in acute and chronic exposure. Human lower airway lung epithelial cells (HSAEC1-KT) will be exposed to MP2.5 and its effect will be evaluated in two periods, 48 h (acute effect) and 4 weeks (chronic effect). Cell viability and proliferation will be assessed using the MTT technique. The gene and protein expression of factors associated with the fibrotic process (TGF-², fibronectin, vimentin, QSMA and collagen), the inflammatory process (p50, p65 and IKKQ) and oxidative stress (SOD1, NOX4 and UCP2) will be evaluated by RT -qPCR and western blot. In the chronic model, the main genetic variants related to lung cancer will be analyzed by next generation sequencing.