Role Of PPAR—γ Agonists In TGF—β Induced Epithelial-Mesenchymal Transition Of Alveolar Epithelial Cells

Idiopathic pulmonary fibrosis is a progressive life-threatening disease without effective therapy. Its pathological character is the fibroblastic foci which comprises of aggregates of mesenchymal cells and extra cellular matrix(ECM). Myofibroblasts are one of the key effector cells in pulmonary fibrosis and are the primary source of ECM. One of the cellular origins of myofibroblast is considered to be pulmonary epithelial cell which go under epithelial mesenchymal transition(EMT) with TGF-β as the most potent activator. Peroxisome-activated receptor-y(PPAR-γ) is a member of the nuclear hormone receptor superfamily the activation of which produces a number of biological effects including alterations in inflammation, metabolism and cell differentiation. The role of PPAR-y as a therapeutic target for fibrotic lung disease has been investigated by several experiments, however mostly focused on fibroblasts differentiation to myofibroblasts. In the present study, human lung epithelial cells A549were examined for morphology change and mesenchymal markers after treated with TGF-β and PPAR-γ. A549cells showed significant decrease on expression of mesenchymal markers with almost none morphology changes by treatment with Rosiglitazone followed with TGF-β compared to treatment with TGF-β alone. PPAR-y expression was down regulated in patients with IPF compared to normal subjects. These observations indicated that PPAR-γ may act as an important regulator in EMT in the lung which suggested a role of PPAR-γ ligands as novel agents for IPF treatment.