Department of Life Science, Dongguk University Biomedi Campus, Goyang, Gyeonggi, 10326, Republic of Korea.
College of Pharmacy, Ewha Womans University, Seoul, 03760, Republic of Korea.
Sci Rep. 2022 Apr 4;12(1):5645. doi: 10.1038/s41598-022-09673-0.
Formaldehyde is a colorless, pungent, highly reactive, and toxic environmental pollutant used in various industries and products. Inhaled formaldehyde is a human and animal carcinogen that causes genotoxicity, such as reactive oxygen species formation and DNA damage. This study aimed to identify the toxic effects of inhaled formaldehyde through an integrated toxicogenomic approach utilizing database information. Microarray datasets (GSE7002 and GSE23179) were collected from the Gene Expression Omnibus database, and differentially expressed genes were identified. The network analyses led to the construction of the respiratory system-related biological network associated with formaldehyde exposure, and six upregulated hub genes (AREG, CXCL2, HMOX1, PLAUR, PTGS2, and TIMP1) were identified. The expression levels of these genes were verified via qRT-PCR in 3D reconstructed human airway tissues exposed to aerosolized formaldehyde. Furthermore, NRARP was newly found as a potential gene associated with the respiratory and carcinogenic effects of formaldehyde by comparison with human in vivo and in vitro formaldehyde-exposure data. This study improves the understanding of the toxic mechanism of formaldehyde and suggests a more applicable analytic pipeline for predicting the toxic effects of inhaled toxicants.
甲醛是一种无色、刺鼻、高反应性和有毒的环境污染物，用于各种工业和产品。吸入的甲醛是一种人类和动物的致癌物质，会导致遗传毒性，如活性氧形成和 DNA 损伤。本研究旨在通过利用数据库信息的综合毒理学方法来识别吸入甲醛的毒性作用。从基因表达综合数据库（GEO）中收集了微阵列数据集（GSE7002 和 GSE23179），并鉴定了差异表达基因。网络分析导致构建了与甲醛暴露相关的呼吸系统相关生物网络，并鉴定了六个上调的枢纽基因（AREG、CXCL2、HMOX1、PLAUR、PTGS2 和 TIMP1）。通过对暴露于雾化甲醛的 3D 重建人气道组织进行 qRT-PCR 验证了这些基因的表达水平。此外，通过与人类体内和体外甲醛暴露数据的比较，NRARP 被新发现为与甲醛的呼吸和致癌作用相关的潜在基因。本研究提高了对甲醛毒性机制的认识，并提出了一种更适用于预测吸入性毒物毒性作用的分析管道。
