银纳米颗粒改变上皮基底膜完整性、细胞黏附分子表达和 TGF-β1 分泌。
Silver nanoparticles alter epithelial basement membrane integrity, cell adhesion molecule expression, and TGF-β1 secretion.
机构信息
Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC, USA.
Molecular Education, Technology and Research Innovation Center, North Carolina State University, Raleigh, NC, USA; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
出版信息
Nanomedicine. 2019 Oct;21:102070. doi: 10.1016/j.nano.2019.102070. Epub 2019 Jul 24.
Silver nanoparticles (AgNPs) are widely used in consumer and pharmaceutical products due to their antipathogenic properties. However, safety concerns have been raised due to their bioactive properties. While reports have demonstrated AgNPs can embed within the extracellular matrix, their effects on basement membrane (BM) production, integrin engagement, and tissue-integrity are not well-defined. This study analyzed the effects of AgNPs on BM production, composition and integrin/focal adhesion interactions in representative lung, esophageal, breast and colorectal epithelia models. A multidisciplinary approach including focused proteomics, QPCR arrays, pathway analyses, and immune-based, structural and functional assays was used to identify molecular and physiological changes in cell adhesions and the BM induced by acute and chronic AgNP exposure. Dysregulated targets included CD44 and transforming growth factor-beta, two proteins frequently altered during pathogenesis. Results indicate AgNP exposure interferes with BM and cell adhesion dynamics, and provide insight into the mechanisms of AgNP-induced disruption of epithelial physiology.
由于具有抗病原体的特性，银纳米粒子（AgNPs）被广泛应用于消费类产品和制药产品。然而，由于其生物活性特性，人们对其安全性提出了担忧。尽管有报道表明 AgNPs 可以嵌入细胞外基质中，但它们对基底膜（BM）产生、整合素结合以及组织完整性的影响尚未得到明确界定。本研究分析了 AgNPs 对代表性肺、食管、乳腺和结直肠上皮模型中 BM 产生、组成和整合素/黏着斑相互作用的影响。采用包括聚焦蛋白质组学、QPCR 阵列、通路分析以及基于免疫的、结构和功能测定在内的多学科方法，鉴定了急性和慢性 AgNP 暴露诱导的细胞黏附和 BM 中分子和生理变化。失调的靶标包括 CD44 和转化生长因子-β，这两种蛋白在发病机制过程中经常发生改变。结果表明，AgNP 暴露会干扰 BM 和细胞黏附动力学，并深入了解了 AgNP 诱导的上皮生理学破坏的机制。
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