Metformin Reduces Inflammation and Lung Fibrosis in a Bleomycin‐Induced Lung Injury Model (LB505)

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by the destruction of lung parenchyma together with deposition of extracellular matrix (ECM) in the interstitial and alveolar spaces. Metformin is developed as an oral anti‐diabetic drug in the biguanide class. Recently, it has been suggested to have anti‐inflammatory and anti‐tissue remodeling effects. Therefore, in this study, we investigated the roles of metformin in bleomycin‐induced lung fibrosis. C57BL/6 mice were intratracheally injected with bleomycin (BLM, 0.2 U/100 μl) on day 0. Metformin was administered orally to the mice once a day from day 1 to day 21. On day 21, the mice were sacrificed. We performed H&E and Masson’s trichrome (MT) staining to evaluate lung inflammation and collagen deposition and analyzed the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) by differential cell counts. From total RNA of lung tissue, the expression level of pro‐collagen, collagen‐1, fibronectin, and tumor growth factor‐β (TGF‐β) was determined by real‐time PCR. Metformin suppressed lung tissue inflammation in BLM‐instilled mice on day 21. Consistent with this, the number of inflammatory cells in BALF was diminished by metformin treatment. BLM increased the level of pro‐collagen, collagen‐1, fibronectin, and TGF‐β mRNA expression on day 21, which was suppressed in metformin‐treated mice. Metformin reduced peribronchial collagen deposition induced by BLM on day 21. Metformin has protective effects on BLM‐induced lung inflammation and remodeling.