Effect of extracellular matrix protection factor-3, a novel inhibitor of matrix metalloprotease-12, on transforming growth factor-beta production in pulmonary fibrosis diseased fibroblasts
Location
Philadelphia, PA
Start Date
17-4-2026 1:30 PM
End Date
17-4-2026 2:30 PM
Description
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and a significant incurable global health burden. COPD refers to a group of diseases that cause blockage of airflow and breathing-related issues. Transforming growth factor-β (TGF-β) production and endogenous activation are crucial events in the progression of pulmonary fibrosis as a subset of COPD. TGF-β is considered a potent inducer of collagen production and other extracellular matrix (ECM) proteins, leading to the progression of pulmonary fibrosis. In addition to the overexpression and endogenous activation of TGF-β, matrix metalloprotease (MMP)-12 is upregulated in the pathogenesis of pulmonary fibrosis, leading to ECM dysregulation.
OBJECTIVE: Despite the importance of both TGF-β and MMPs in the pathogenesis of pulmonary fibrosis, little is known about the effects of inhibiting MMP-12 on endogenous TGF-β activation.
METHOD: Diseased Human Lung Fibroblast (DHLFB) primary cells were cultured in monolayer and were either treated with serum free media or serum free media containing 10-50 µg of a novel MMP-12 inhibitor, Extracellular Matrix Protection Factor (ECPF)-3, for 24 hours. The presence in secreted and extracellular matrix incorporated fractions of total TGF-β production and endogenous TGF-β activation were determined via enzyme-linked immunosorbent assays.
RESULTS: DHLFB cells produced more total TGF-β in serum-free cultures than normal controls (DHLFB 109pg/culture versus NHLFB 30.93pg/culture). In addition, DHLFB cells produced a larger amount of endogenously activated TGF-β (DHLFB 18.7pg/culture versus NHLFB 3.09pg/culture), reflecting their diseased profile. Treatment of DHLFB cells with 10-50ug ECPF-3 for 24 hours in serum-free media resulted in an increase in incorporated TGF-β, both total and endogenously activated (p< 0.001 for each) while the secreted fractions were unchanged.
CONCLUSION: Our results suggest that inhibiting MMP-12 in DHLFB cells alters the activation state and storage of TGF-β. In previous studies, we have shown that ECPF-3 decreases elastin degradation and collagen production. Overall, these results indicate the potential for ECPF-3 to act as a therapeutic in slowing the progression of pulmonary fibrosis in diseased fibroblasts.
Embargo Period
5-21-2026
Effect of extracellular matrix protection factor-3, a novel inhibitor of matrix metalloprotease-12, on transforming growth factor-beta production in pulmonary fibrosis diseased fibroblasts
Philadelphia, PA
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and a significant incurable global health burden. COPD refers to a group of diseases that cause blockage of airflow and breathing-related issues. Transforming growth factor-β (TGF-β) production and endogenous activation are crucial events in the progression of pulmonary fibrosis as a subset of COPD. TGF-β is considered a potent inducer of collagen production and other extracellular matrix (ECM) proteins, leading to the progression of pulmonary fibrosis. In addition to the overexpression and endogenous activation of TGF-β, matrix metalloprotease (MMP)-12 is upregulated in the pathogenesis of pulmonary fibrosis, leading to ECM dysregulation.
OBJECTIVE: Despite the importance of both TGF-β and MMPs in the pathogenesis of pulmonary fibrosis, little is known about the effects of inhibiting MMP-12 on endogenous TGF-β activation.
METHOD: Diseased Human Lung Fibroblast (DHLFB) primary cells were cultured in monolayer and were either treated with serum free media or serum free media containing 10-50 µg of a novel MMP-12 inhibitor, Extracellular Matrix Protection Factor (ECPF)-3, for 24 hours. The presence in secreted and extracellular matrix incorporated fractions of total TGF-β production and endogenous TGF-β activation were determined via enzyme-linked immunosorbent assays.
RESULTS: DHLFB cells produced more total TGF-β in serum-free cultures than normal controls (DHLFB 109pg/culture versus NHLFB 30.93pg/culture). In addition, DHLFB cells produced a larger amount of endogenously activated TGF-β (DHLFB 18.7pg/culture versus NHLFB 3.09pg/culture), reflecting their diseased profile. Treatment of DHLFB cells with 10-50ug ECPF-3 for 24 hours in serum-free media resulted in an increase in incorporated TGF-β, both total and endogenously activated (p< 0.001 for each) while the secreted fractions were unchanged.
CONCLUSION: Our results suggest that inhibiting MMP-12 in DHLFB cells alters the activation state and storage of TGF-β. In previous studies, we have shown that ECPF-3 decreases elastin degradation and collagen production. Overall, these results indicate the potential for ECPF-3 to act as a therapeutic in slowing the progression of pulmonary fibrosis in diseased fibroblasts.