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首页> 外文期刊>The Journal of Nutritional Biochemistry >Zinc salicylate reduces airway smooth muscle cells remodelling by blocking mTOR and activating p21(Waf1/Cip1)
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Zinc salicylate reduces airway smooth muscle cells remodelling by blocking mTOR and activating p21(Waf1/Cip1)

机译：Saticylate锌通过阻断MTOR和活化P21减少气道平滑肌细胞重塑（WAF1 / CIP1）

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摘要

Asthma is characterized by chronic inflammation and tissue remodeling of the airways. Remodeling is resistant to pharmaceutical therapies. This study investigated the effect of zinc salicylate-methylsulfonylmethane (Zn-Sal-MSM) compared to zinc salicylate (Zn-Sal), or sodium salicylate (Na-Sal), or zinc chloride (ZnCl2) on remodeling parameters of human airway smooth muscle cells (ASMC). Human ASMC obtained from asthma patients ( n = 7) and nonasthma controls ( n = 7) were treated with one of the reagents. Cell proliferation and viability was determined by direct cell counts and MTT assay. The expression of and phosphorylation proteins was determined by Western-blotting, ELISA, immunofluorescence, and mass spectrometry. Extracellular matrix deposition by ELISA. Zn-Sal-MSM, Zn-Sal and Na-Sal (0.1-100 mu g/mL) significantly reduced PDGF-BB-induced proliferation in a concentration dependent manner, while ZnCl2 was toxic. The reduced proliferation correlated with increased expression of the cell cycle inhibitor p21(Waf1/Cip1), and reduced activity of Akt, p70S6K, and Erk1/2. Zn-Sal-MSM, Zn-Sal, but not Na-Sal reduced the deposition of fibronectin and collagen type-I. Furthermore, Zn-Sal-MSM reduced the mitochondria specific COX4 expression. Mass spectrometry indicated that Zn-Sal-MSM modified the expression of several signaling proteins and zincdependent enzymes. In conclusion, Zn-Sal-MSM and Zn-Sal potentially prevent airway wall remodeling in asthma by inhibition of both the Erk1/2 and mTOR signaling pathways. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
机译：哮喘的特点是气道的慢性炎症和组织重塑。重塑对药物疗法有抵抗力。本研究比较了水杨酸锌（Zn-Sal）、水杨酸钠（Na-Sal）或氯化锌（ZnCl2）与水杨酸锌（Zn-Sal-MSM）对人气道平滑肌细胞（ASMC）重塑参数的影响。从哮喘患者（n=7）和非哮喘对照组（n=7）获得的人ASMC用其中一种试剂治疗。通过直接细胞计数和MTT法测定细胞增殖和活力。蛋白和磷酸化蛋白的表达通过Western印迹、ELISA、免疫荧光和质谱测定。ELISA检测细胞外基质沉积。Zn-Sal MSM、Zn-Sal和Na-Sal（0.1-100μg/mL）以浓度依赖性方式显著降低PDGF-BB诱导的增殖，而ZnCl2具有毒性。增殖减少与细胞周期抑制剂p21（Waf1/Cip1）表达增加以及Akt、p70S6K和Erk1/2活性降低相关。Zn-Sal-MSM，Zn-Sal，而不是Na-Sal降低了纤维连接蛋白和I型胶原的沉积。此外，Zn-Sal-MSM降低了线粒体特异性COX4的表达。质谱分析表明，Zn-Sal MSM修饰了几种信号蛋白和锌依赖酶的表达。总之，Zn-Sal-MSM和Zn-Sal可能通过抑制Erk1/2和mTOR信号通路来预防哮喘患者的气道壁重塑。（c） 2020年，作者。由爱思唯尔公司出版。这是一篇基于CC by-NC-ND许可证的开放获取文章（http://creativecommons.org/licenses/by-nc-nd/4.0/ )

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