The role of free fatty acids in idiopathic pulmonary fibrosis

Abstract

Introduction: Dysregulation of the lipid metabolism has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF);however, the role of free fatty acids (FFA) is not well defined. Aim: to investigate the role of FFA in the pathogenesis in IPF Methods: Fatty acid methyl esters were analyzed with Agilent 7890/5975 Gas Chromatography-Mass Spectrometry and HP-5 MS 30 m * 250 µm * 0.25 µm column (Agilent 19091S-433) in the lung tissues of controls (n=10) and IPF patients (n=10). To evaluate the function of FFA, human lung fibroblasts (MRC-5 cells) were treated with TGF-s1 (5 ng/ml) and/or FFAs including palmitic acid, stearic acid, oleic acid and linoleic acid. Cell viability and protein expression were measured via MTT assay and western blot analysis, respectively. Results: Although the levels of palmitic acid, oleic acid and linoleic acid were elevated, the level of stearic acid was significantly reduced in the lung tissues of patients. Palmitic acid, oleic acid or linoleic acid significantly enhanced the TGF-s1 induced expression of α-smooth muscle actin (SMA) and collagen type-1 in MRC-5 cells;however, stearic acid significantly reduced them. Moreover, palmitic acid and linoleic acid increased the TGF-s1 induced proliferation of MRC-5 cells, but stearic acid decreased it. Stearic acid significantly inhibited the levels of p-Smad2/3 in MRC-5 cells treated with TGF-s1. Conclusion: Our findings suggest that FFAs may have effects on pulmonary fibrosis by regulating TGF-s1 induced activation and proliferation of fibroblasts and be implicated as potential therapeutic targets in IPF.