Therapeutic effects of TMF and catechol in pulmonary fibrosis: in vitro and in vivo analysis

Abstract

Idiopathic pulmonary fibrosis is a fatal lung disorder characterized by abnormal deposition of extracellular matrix (ECM), which is secreted by activated myofibroblasts. While the origin of myofibroblasts has been discussed, epithelial-mesenchymal transition (EMT) is being noticed as one of the mechanisms of myofibroblast activation. Recent studies have shown that reactive oxygen species appear to induce not only EMT but also fibrotic progression and maintenance. Therefore, we tested chemicals that have antioxidant capacity as drugs for fibrosis. To evaluate the effects of 4′,6,7-trimethoxyisoflavone (TMF) and catechol (CAT) on EMT and fibrosis, we used an in vitro transforming growth factor (TGF)-β1 or bleomycin-induced model and an in vivo BLM-induced model. The results showed that the co-administration of TMF/CAT ameliorated pulmonary fibrosis by decreasing EMT and ECM accumulation by hindering both Smad and non-Smad TGF-β signalling cascades. Furthermore, significant increases in the number of total immune cells (especially lymphocytes) were observed in BLM-treated animals treated with TMF/CAT. Our findings suggest that co-intervention with TMF/CAT may be a potential treatment for fibrosis.