Study of extracelular matrix fiber constituints and the expression of metaloproteases during emphysema development induced by elastase in mice

• Grant number: 11/08584-6
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2011
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Grantee: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

COPD is the fourth leading cause of mortality in the world and an important cause of chronic morbidity, which is correlated with significant disability and reduced quality of life for their patients and high costs to public health. In emphysema, the lung parenchyma (including the components of the extracellular matrix) is in a constant process of destruction and remodeling, leading to major changes in the mechanical and structural properties of the tissue. Whereas experimental studies of emphysema have demonstrated an increased deposition of collagen fibers and elastic after the disease development ( 21 days after instillation), we intend, in this study, to evaluate the extracellular matrix components of parenchyma, in the early hours (1, 3 and 6h) 3 and 21 days after the disease induction to detect if at any time prior to 21 days there was a reduction in these fibers. For that, C57BL / 6 will be submitted to a protocol of pulmonary emphysema by intranasal instillation of porcine pancreatic elastase (0.667 IU) and these animals will be sacrificed at different times: 1, 3, 6 hours, 3 and 21 days after instillation. The control groups will receive the same treatment with saline (NaCl 0.9%). In different times, the animals will be anesthetized and sacrificed. Lungs will be removed and sectioned for specific stainings to quantify the mean linear intercept, the volume proportion of collagen type I and III, elastin and fibrillin. We will also assess the gene expression of different MMPs (MMP-1, MMP-8, MMP-12 and MMP-13). (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)

ROBERTONI, FABOLA S. Z.; OLIVO, CLARICE R.; LOURENCO, JULIANA D.; GONCALVES, NATALIA G.; VELOSA, ANA PAULA P.; LIN, CHIN J.; FLO, CLAUDIA M.; SARAIVA-ROMANHOLO, BEATRIZ M.; SASAKI, SERGIO D.; MARTINS, MILTON A.; et al. Collagenase mRNA Overexpression and Decreased Extracellular Matrix Components Are Early Events in the Pathogenesis of Emphysema. PLoS One, v. 10, n. 6, JUN 8 2015. (12/02957-8, 11/08584-6)