West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA.
National Institute for Occupational and Environmental Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505, USA.
Int J Mol Sci. 2019 May 29;20(11):2635. doi: 10.3390/ijms20112635.
As the demand for multi-walled carbon nanotube (MWCNT) incorporation into industrial and biomedical applications increases, so does the potential for unintentional pulmonary MWCNT exposure, particularly among workers during manufacturing. Pulmonary exposure to MWCNTs raises the potential for development of lung inflammation, fibrosis, and cancer among those exposed; however, there are currently no effective biomarkers for detecting lung fibrosis or predicting the risk of lung cancer resulting from MWCNT exposure. To uncover potential mRNAs and miRNAs that could be used as markers of exposure, this study compared in vivo mRNA and miRNA expression in lung tissue and blood of mice exposed to MWCNTs with in vitro mRNA and miRNA expression from a co-culture model of human lung epithelial and microvascular cells, a system previously shown to have a higher overall genome-scale correlation with mRNA expression in mouse lungs than either cell type grown separately. Concordant mRNAs and miRNAs identified by this study could be used to drive future studies confirming human biomarkers of MWCNT exposure. These potential biomarkers could be used to assess overall worker health and predict the occurrence of MWCNT-induced diseases.
随着多壁碳纳米管(MWCNT)在工业和生物医学应用中的需求增加,无意吸入肺内 MWCNT 的潜在风险也随之增加,尤其是在制造过程中的工人。肺内暴露于 MWCNTs 可能导致暴露人群发生肺炎症、纤维化和癌症;然而,目前尚无有效的生物标志物来检测肺纤维化或预测 MWCNT 暴露导致肺癌的风险。为了揭示可能作为暴露标志物的潜在 mRNAs 和 miRNAs,本研究比较了暴露于 MWCNTs 的小鼠肺组织和血液中的体内 mRNA 和 miRNA 表达,以及先前已显示与人肺上皮和微血管细胞共培养模型中的体外 mRNA 和 miRNA 表达的相关性,与单独培养的任何一种细胞类型相比,该系统与小鼠肺部的整体基因组规模相关性更高。通过本研究鉴定的一致的 mRNAs 和 miRNAs 可用于驱动未来的研究,以确认 MWCNT 暴露的人类生物标志物。这些潜在的生物标志物可用于评估工人的整体健康状况并预测 MWCNT 诱导疾病的发生。