To Study the Anti-Proliferative Effect of Pirfenidone via MAP Kinase Signaling Pathway

Abstract

Pirfenidone is a pyridine chemical compound used as a therapeutic drug used for the treatment of Idiopathic Pulmonary Fibrosis (IPF). The characteristic feature of the fibrosis is the deposition of extracellular matrix protein in the lungs and ultimate lead to the failure of the organ. Pirfenidone is an orally active small molecular comprising a modified phenyl pyridine that have been shown to inhibit the progression of fibrosis in animal model and in patient with IPF. The compound exhibits well?documented anti-fibrotic and anti? inflammatory activities but its molecular target has not been elucidated. Pirfenidone is a broad-spectrum anti-fibrotic drug with the ability to decreases the PDGF, TGF-?, TNF-? and COL (collagen). After treating A549 cell line with Pirfenidone with different concentrations and different time interval, cell viability was measured by the MTT assay. Pirfenidone cause the cytotoxicity in model A549 cell line and anti-proliferation through different Smad dependent and independent pathway. Pirfenidone treatment was given to check downstream signaling pathway i.e. MAP kinase activity dependent. Although previous studies have shown that Pirfenidone is associated with renal fibrosis in TGF??1 expression the mechanism remains poorly understood. Taken into account these, we hypothesized that pirfenidone may have an anti?fibrotic effect through antagonizing the MAPK signaling pathway.