24 - Extracellular Matrix Protection factor-2, a Novel Matrix metalloprotease-8 Inhibitor, Increases Elastin Incorporation into the Extracellular Matrix of Fibroblasts Isolated from Pulmonary Fibrosis Patients
Saturday, March 23, 2024
5:00pm – 7:00pm US EDT
Location: Sheraton Hall
Poster Board Number: 24
There are separate poster presentation times for odd and even posters.
Odd poster #s – first hour
Even poster #s – second hour
Student Researcher PCOM Philadelphia, Pennsylvania, United States
Abstract Body : Pulmonary fibrosis is a subset of chronic obstructive pulmonary disease (COPD). It is characterized by the removal of elastin in the alveoli and resultant fibrotic deposition of collagen. The end result is that the walls of the lung’s air spaces lose their elasticity. The family of matrix metalloproteases (MMPs) is one of the players contributing to this irregular extracellular matrix metabolism in the disease. MMP-8, a collagenase, has been shown to increase fibrosis by an abnormal deposition of collagen type I during pulmonary fibrosis. Previously, this group has demonstrated that a novel inhibitor of MMP-8, the Extracellular Matrix Protection Factor-2 (ECPF-2), can slow the deposition of collagen type I in primary cultures of human lung fibroblasts collected from patients with pulmonary fibrosis. In this study, we investigate the effects of ECPF-2 inhibition of MMP-8 in elastin production. Elastin is the main extracellular matrix protein that gives the alveolar walls their elastic properties. Its production and degradation are further regulated by transforming growth factor beta (TGF-b) and its storage molecule, latent transforming growth factor beta binding protein (LTBP-1). Others have demonstrated that during pulmonary fibrosis, degradation of elastin increases and production of LTBP-1 decreases, leading to more active TGF-b and the concomitant increase in the fibrotic response. ECPF-2 treatment (10ug/ml for 24 hours in serum-free media) of primary cultures of human lung fibroblasts, isolated from pulmonary fibrosis diseased lungs, resulted in a 4.63% decrease in secreted elastin and an 8.90% increase in elastin incorporation into the extracellular matrix. In addition, 10ug ECPF-2 treatment reduced secretion of LTBP-1 by 70% and increased incorporation into the extracellular matrix by 25%. This indicates that TGF-b is being stored instead of activated by the cells. We are currently measuring endogenous TGF-b production and activation to determine the correlation between ECPF-2 effects on LTBP-1 and pulmonary fibrosis through the TGF-b pathway. These data suggest that inhibition of ECPF-2, a collagenase, can decrease the symptoms of extracellular matrix degradation associated with pulmonary fibrosis in COPD.
