Temporal profile of metaloproteases gene expression in elastase-induced emphysema

Ever since protease anti-protease hypothesis has prevailed as the major role for the emphysema development, experimental models have been examined the role of the metoproteases (MMPs) in alveolar destruction. However, few studies have evaluated the collagenases effects at the early hours after the disease induction. Objectives: To describe the progression of parenchymal destruction and the collagenases expression at the beginning of the emphysema development. Methods: 80 C57BL/6 received intranasal instillation of porcine pancreatic elastase (PPE Group) or saline solution (S group). Animals were anesthetized, euthanized at: 1, 3, 6 hours, 3 and 21 days after instillation and their lungs removed to quantify the mean linear intercept (Lm) and the volume proportion of collagen type I in parenchyma. Also, we used the Real-time PCR to assess the gene expression of MMP-1, -8 and -13. Results: Compared to S group in each time, MMP-13 gene expression was increased in PPE mice since 1h after instillation and it remained elevated until 6h, whereas the MMP8 gene expression was increased after 6h of emphysema induction. There was no increase in MMP-1a and MMP-1b gene expression. Although, we observed an increase in Lm since 3h, the higher values were observed at 3 and 21 days suggesting a progression in alveolar enlargement. Also, we observed a decrease in collagen type I in parenchyma only at 3d while at the 21d these values returned to values similar to the S Group. Conclusions: Our results showed the importance of the MMP-8 and MMP-13 activity since the first hours after the emphysema induction, testifying the importance of collagenases in protease-antiprotease imbalance and emphysema progression.