Journal
RESPIROLOGY
Volume 26, Issue 3, Pages 255-263Publisher
WILEY
DOI: 10.1111/resp.13949
Keywords
fatty acid; idiopathic pulmonary fibrosis; metabolomics; non-esterified; therapy
Categories
Funding
- National Research Foundation of Korea (NRF) - Ministry of Science and ICT [NRF-2016R1A2B4016318, NRF-2019R1A2C2008541]
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea [18-495]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) [2016R1D1A1B03935517, 2017R1D1A1B03030214]
- Asan Bio-Resource Center [2014-13(82)]
- Chungnam National University Hospital, Korea Biobank Network [2016-1366]
- National Research Foundation of Korea [2017R1D1A1B03030214, 2016R1D1A1B03935517] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This study identified lower levels of stearic acid in lung tissues of IPF patients and demonstrated its important role in inhibiting fibrotic marker expression and modulating profibrotic signaling. Stearic acid also exhibited antifibrotic effects in a mouse model of lung fibrosis.
Background and objective Lipid metabolism dysregulation has been implicated in the pathogenesis of IPF; however, the roles of most lipid metabolites in lung fibrosis remain unexplored. Therefore, we aimed to identify changes in lipid metabolites in the lung tissues of IPF patients and determine their roles in pulmonary fibrosis. Methods Free fatty acids in the lung tissues of IPF patients and controls were quantified using a metabolomic approach. The roles of free fatty acids in fibroblasts or epithelial cells treated with TGF-beta 1 were evaluated using fibrotic markers. The antifibrotic role of stearic acid was also assessed in a bleomycin-induced lung fibrosis mouse model. Protein levels in cell lysates or tissues were measured by western blotting. Results The levels of stearic acid were lower in IPF lung tissues than in control lung tissues. Stearic acid significantly reduced TGF-beta 1-induced alpha-SMA and collagen type 1 expression in MRC-5 cells. Furthermore, stearic acid decreased the levels of p-Smad2/3 and ROS in MRC-5 cells treated with TGF-beta 1 and disrupted TGF-beta 1-induced EMT in Beas-2B cells. Stearic acid reduced the levels of bleomycin-induced hydroxyproline in a mouse model. Conclusion Changes in the free fatty acid profile, including low levels of stearic acid, were observed in IPF patients. Stearic acid may exert antifibrotic activity by regulating profibrotic signalling.
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