SILAC-based proteomic profiling of the suppression of TGF-β1-induced lung fibroblast-to-myofibroblast differentiation by trehalose
SILAC-based proteomic profiling of the suppression of TGF-β1-induced lung fibroblast-to-myofibroblast differentiation by trehalose
复制标题
海藻糖抑制 TGF-β1 诱导的肺成纤维细胞向肌成纤维细胞分化的基于 SILAC 的蛋白质组学分析
DOI：
10.1016/j.taap.2020.114916
复制
发表时间：
2020-03-15
影响因子：
3.8
通讯作者：
Jiang, Xiaogang
中科院分区：
文献类型：
--
作者：
Lu, Fanqing;Sun, Xionghua;Jiang, Xiaogang
成纤维细胞向肌成纤维细胞分化是肺纤维化最重要的特征之一，筛选针对成纤维细胞分化的天然化合物一直是发现治疗肺纤维化候选药物的有希望的方法。据报道海藻糖有许多潜在的医学应用，特别是在治疗神经退行性疾病方面。然而，海藻糖是否抑制肺成纤维细胞分化尚不清楚。在这项工作中，我们发现海藻糖在诱导转化生长因子β 1 （tgf - β 1）后降低了预处理组、联合治疗组和治疗后组α -平滑肌肌动蛋白（α - sma）的表达水平。海藻糖还降低了tgf - β 1刺激的MRC-5细胞中I型胶原蛋白的产生、含肺成纤维细胞凝胶的收缩性和细胞丝的形成。虽然海藻糖是一种已知的自噬诱导剂，但我们的研究结果表明它对成纤维细胞分化的抑制作用不是通过海藻糖诱导的自噬来实现的。不影响典型TGF β /Smad2/3通路。通过应用蛋白质组学分析技术，我们证明β -连环蛋白的下调参与了海藻糖抑制成纤维细胞分化的作用。β -连环蛋白激动剂SKL2001逆转了海藻糖对成纤维细胞分化的抑制作用。综上所述，这些实验表明海藻糖通过下调β -catenin抑制成纤维细胞分化，而不是通过典型自噬和TGF β /Smad2/3途径抑制成纤维细胞分化，这不仅是对海藻糖的新认识，而且对未来海藻糖对肺纤维化的体内研究也有很大帮助。
Fibroblast-to-myofibroblast differentiation is one of the most important characteristics of pulmonary fibrosis, and screening natural compounds targeting fibroblast differentiation is always a promising approach to discover drug candidates for treatment of pulmonary fibrosis. Trehalose reportedly has many potential medical applications, especially in treating neurodegeneration diseases. However, it remains unclear whether trehalose suppresses lung fibroblast differentiation. In this work, we found that trehalose decreased the expression levels of alpha-smooth muscle actin (alpha-SMA) following the induction of transforming growth factor beta 1 (TGF-beta 1) in pretreatment, co-treatment, and post-treatment groups. Trehalose also reduced the production of type I collagen, lung fibroblast-containing gel contractility and cell filament formation in TGF-beta 1-stimulated MRC-5 cells. Although trehalose is a known autophagy inducer, our results showed that its suppressive effect on fibroblast differentiation was not via trehalose-induced autophagy. And it did not affect canonical TGF beta/Smad2/3 pathway. By applying proteomic profiling technology, we demonstrated that the downregulation of beta-catenin was involved in the trehalose-repressive action on fibroblast differentiation. The beta-catenin agonist, SKL2001, reversed the suppressive effect of trehalose on fibroblast differentiation. Overall, these experiments demonstrated that trehalose suppressed fibroblast differentiation via the downregulation of beta-catenin, but not through canonical autophagy and TGF beta/Smad2/3 pathway, which is not only a novel understanding of trehalose, but also quite helpful for in vivo research of trehalose on pulmonary fibrosis in future.