Therapeutic Potential of Lentiviral miR ‐200a Mimics in Regulating Fibrinolysis and EMT Markers During Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the excessive accumulation of collagen‐rich extracellular matrix (ECM), leading to the replacement of normal lung architecture. This pathological remodeling is primarily caused by the epithelial‐to‐mesenchymal transition (EMT), in which epithelial cells lose their polarity and adhesion and acquire mesenchymal characteristics that encourage the deposition of ECM and the growth of fibrotic tissue. The disruption of ECM homeostasis caused by dysregulated MMP‐2 and MMP‐9 activity in IPF paradoxically promotes abnormal tissue remodeling and fibrosis. IPF's unknown etiology, delayed diagnosis, and lack of effective treatments point to a crucial knowledge gap regarding ECM‐ and EMT‐driven fibrosis. The microRNA‐200 (miR‐200) family has been found to be important EMT regulators in recent research, suggesting that they may be able to influence the course of fibrosis. Hereby the current study provides an insight on the role of miR‐200a in regulating MMP‐2 and MMP‐9 in bleomycin (BLM)‐induced lung fibrosis using both in vitro (A549 cells) and in vivo (C57BL/6 mice) models. A549 cells were transfected with a synthetic miR‐200a mimic, and MMP expression was analyzed using RT‐qPCR. In vivo, mice were intranasally administered a lentiviral vector expressing miR‐200a prior to BLM induction, followed by tissue analysis at days 14 and 21 using histological stains and immunofluorescence. Gene and protein expression were quantified via RT‐qPCR and western blotting. Our findings indicate that miR‐200a mitigates fibrosis by downregulating MMPs and PAI‐1 while upregulating uPA and uPAR, suggesting a protective role of miR‐200a and its potential as a therapeutic target for pulmonary fibrosis.