Stearic acid attenuates profibrotic signalling in idiopathic pulmonary fibrosis
Stearic acid attenuates profibrotic signalling in idiopathic pulmonary fibrosis
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DOI：
10.1111/resp.13949
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发表时间：
2020-10-06
期刊：
影响因子：
6.9
通讯作者：
Song, Jin Woo
中科院分区：
文献类型：
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作者：
Kim, Hak-Su;Yoo, Hyun Ju;Song, Jin Woo
背景与目的脂质代谢失调与IPF的发病机制有关；然而，大多数脂质代谢物在肺纤维化中的作用仍未被探索。因此，我们旨在确定IPF患者肺组织中脂质代谢物的变化，并确定其在肺纤维化中的作用。方法采用代谢组学方法对IPF患者和对照组肺组织中的游离脂肪酸进行定量分析。使用纤维化标记物评估游离脂肪酸在tgf - β 1处理的成纤维细胞或上皮细胞中的作用。硬脂酸的抗纤维化作用也在博莱霉素诱导的肺纤维化小鼠模型中进行了评估。western blotting检测细胞裂解液或组织中的蛋白水平。结果IPF肺组织中硬脂酸水平低于对照组肺组织。硬脂酸显著降低tgf - β 1诱导的α - sma和MRC-5细胞中1型胶原蛋白的表达。此外，硬脂酸降低了tgf - β 1处理的MRC-5细胞中p-Smad2/3和ROS的水平，并破坏了tgf - β 1诱导的Beas-2B细胞中的EMT。硬脂酸在小鼠模型中降低了博莱霉素诱导的羟脯氨酸水平。结论IPF患者游离脂肪酸谱发生变化，包括硬脂酸水平降低。硬脂酸可能通过调节促纤维化信号传导发挥抗纤维化作用。
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.