SILAC-based proteomic profiling of the suppression of TGF-β1-induced lung fibroblast-to-myofibroblast differentiation by trehalose.,Toxicology and Applied Pharmacology

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SILAC-based proteomic profiling of the suppression of TGF-β1-induced lung fibroblast-to-myofibroblast differentiation by trehalose.
Toxicology and Applied Pharmacology ( IF 3.3 ) Pub Date : 2020-02-07 , DOI: 10.1016/j.taap.2020.114916
Fanqing Lu ₁ , Xionghua Sun ₁ , Xiafang Xu ₁ , Xiaogang Jiang ₁

Affiliation

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 α-smooth muscle actin (α-SMA) following the induction of transforming growth factor β1 (TGF-β1) 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-β1-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 TGFβ/Smad2/3 pathway. By applying proteomic profiling technology, we demonstrated that the downregulation of β-catenin was involved in the trehalose-repressive action on fibroblast differentiation. The β-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 β-catenin, but not through canonical autophagy and TGFβ/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.

中文翻译：

海藻糖可抑制SILAC的蛋白质组分析，从而抑制TGF-β1诱导的肺成纤维细胞向肌成纤维细胞分化。

成纤维细胞向肌成纤维细胞的分化是肺纤维化的最重要特征之一，筛选靶向成纤维细胞的天然化合物一直是寻找治疗肺纤维化候选药物的有前途的方法。据报道海藻糖具有许多潜在的医学应用，尤其是在治疗神经退行性疾病方面。然而，目前尚不清楚海藻糖是否抑制肺成纤维细胞分化。在这项工作中，我们发现海藻糖在预处理，联合治疗和后处理组中诱导了转化生长因子β1（TGF-β1）的作用后降低了α平滑肌肌动蛋白（α-SMA）的表达水平。海藻糖还减少了I型胶原的产生，TGF-β1刺激的MRC-5细胞中含肺成纤维细胞的凝胶收缩力和细胞丝形成。尽管海藻糖是已知的自噬诱导物，但我们的结果表明，其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。并且它不影响典型的TGFβ/ Smad2 / 3途径。通过应用蛋白质组分析技术，我们证明了β-catenin的下调参与了对成纤维细胞分化的海藻糖抑制作用。β-catenin激动剂SKL2001逆转了海藻糖对成纤维细胞分化的抑制作用。总体而言，这些实验表明，海藻糖可通过下调β-连环蛋白抑制成纤维细胞分化，但不能通过自噬和TGFβ/ Smad2 / 3途径抑制，这不仅是对海藻糖的新认识，

更新日期：2020-02-07

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