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Air Pollution Autophagy and Skin Aging: Impact of Particulate Matter (PM10) on Human Dermal Fibroblasts

机译:空气污染自噬和皮肤老化:颗粒物质(PM10)对人皮肤成纤维细胞的影响

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摘要

A World Health Organization (WHO) report from 2016 states that over 3 million people die annually from air pollution, which places air pollution as the world’s largest single environmental health risk factor. Particulate matter (PM) is one of the main components of air pollution, and there is increasing evidence that PM exposure exerts negative effects on the human skin. To see the impact of air pollution on skin aging, we analyzed the effect of PM exposure on human dermal fibroblasts (HDFs) with Western blot, enzyme-linked immunosorbent assay (ELISA), and gene analysis. Cultured HDFs were exposed to PM10 at a concentration of 30 µg/cm2 for 24 h, and their gene/protein expression of inflammatory cytokines, fibroblast chemical mediators, and autophagy were assessed. A total of 1977 genes were found to be differentially expressed following PM exposure. We observed a significantly increased expression of pro-inflammatory genes interleukin (IL)-1β, IL-6, IL-8 and IL-33 in dermal fibroblasts exposed to PM10. Protein expression of IL-6 and IL-8 also significantly increased, which complemented our gene analysis results. In addition, there was a significant increase in cytochrome P450 (CYP1A1, CYP1B1), matrix metalloproteinase (MMP-1, MMP-3) mRNA expression, and significant decrease in transforming growth factor (TGF)-β, collagen type I alpha chain (COL1A1, COL1A2), and elastin (ELN) mRNA expression in PM-exposed dermal fibroblasts. Protein expression of MMP-1 was significantly increased and that of TGF-β and procollagen profoundly decreased, similar to the gene analysis results. Autophagy, an integrated cellular stress response, was also increased while transmission electron microscopy (TEM) analysis provided evidence of PM internalization in the autolysosomes. Taken together, our results demonstrate that PM10 contributes to skin inflammation and skin aging via impaired collagen synthesis. Increased autophagy in our study suggests a reparative role of autophagy in HDFs stressed with PM, but its biological significance requires further research.
机译:世界卫生组织(WHO)2016年的一份报告指出,每年有超过300万人死于空气污染,这使空气污染成为世界上最大的单一环境健康风险因素。颗粒物(PM)是空气污染的主要成分之一,越来越多的证据表明PM暴露会对人体皮肤产生负面影响。为了了解空气污染对皮肤衰老的影响,我们通过蛋白质印迹,酶联免疫吸附测定(ELISA)和基因分析分析了PM暴露对人皮肤成纤维细胞(HDF)的影响。将培养的HDFs暴露于浓度为30 µg / cm 2 的PM10中24 h,并评估其炎症细胞因子,成纤维细胞化学介质和自噬的基因/蛋白质表达。发现共有1977个基因在PM暴露后差异表达。我们观察到暴露于PM10的皮肤成纤维细胞中促炎基因白介素(IL)-1β,IL-6,IL-8和IL-33的表达显着增加。 IL-6和IL-8的蛋白质表达也显着增加,这补充了我们的基因分析结果。此外,细胞色素P450(CYP1A1,CYP1B1),基质金属蛋白酶(MMP-1,MMP-3)mRNA表达显着增加,而转化生长因子(TGF)-β,I型胶原α链显着减少( PM暴露的真皮成纤维细胞中的COL1A1,COL1A2和弹性蛋白(ELN)mRNA表达。与基因分析结果相似,MMP-1的蛋白表达显着增加,而TGF-β和前胶原的蛋白表达则显着下降。自噬是一种综合的细胞应激反应,同时透射电子显微镜(TEM)分析提供了自溶酶中PM内在化的证据。两者合计,我们的结果表明PM10通过受损的胶原蛋白合成促进皮肤炎症和皮肤老化。自噬在我们的研究中增加表明自噬在受PM胁迫的HDF中具有修复作用,但其生物学意义需要进一步研究。

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