PAI-1 influences and curcumin destabilizes MMP-2, MMP-9 and basement membrane proteins during lung injury and fibrosis

Abstract

One of the characteristic feature of idiopathic pulmonary fibrosis is an imbalanced fibrinolytic system. Plasminogen activator inhibitor-1 (PAI-1), an essential serine protease in the fibrinolytic system, has an anti-fibrotic tendency in some organs and a pro-fibrotic nature in others. Curcumin is reported to regulate the fibrinolytic system. In this study, we sought to determine how curcumin affected alterations in tissue remodelling mediated by PAI-1 in lung fibrosis. For in vitro studies, NIH3T3 fibroblasts were either exposed to TGF-β or overexpressed with PAI-1, and/or treated with curcumin. For in vivo studies, C57BL/6 mice were either instilled with bleomycin, overexpressed with PAI-1, and/or intervened with curcumin. Protein and gene expression studies were performed by western blotting and RT-PCR techniques, respectively. Curcumin intervention, in vitro and in vivo, could inhibit the the expression of collagen, fibronectin, MMP-2, and MMP-9, which was otherwise elevated by TGF-β or bleomycin. In conclusion, curcumin reduces pulmonary fibrosis by suppressing excessive basement membrane protein deposition and, likely, preventing the thickening of the alveolar septum.