PMID- 38165020 OWN - NLM STAT- MEDLINE DCOM- 20240311 LR - 20240311 IS - 1522-7278 (Electronic) IS - 1520-4081 (Linking) VI - 39 IP - 4 DP - 2024 Apr TI - A transcriptomics-based investigation of the mechanism of pulmonary fibrosis induced by nickel oxide nanoparticles. PG - 2374-2389 LID - 10.1002/tox.24088 [doi] AB - Nickel oxide nanoparticles (NiONPs) are an emerging nanomaterial, which poses a huge threat to the health of workplace population. Nanoparticles induce pulmonary fibrosis, and its mechanisms are associated with noncoding RNAs (ncRNAs). However, ncRNAs and competing endogenous RNA (ceRNA) networks which involved in NiONP-induced pulmonary fibrosis are still unclear. This study aimed to identify ncRNA-related ceRNA networks and investigate the role of the Wnt/beta-catenin pathway in pulmonary fibrosis. Male Wistar rats were intratracheally instilled with 0.015, 0.06, and 0.24 mg/kg NiONPs twice a week for 9 weeks. First, we found there were 93 circularRNAs (circRNAs), 74 microRNAs (miRNAs), 124 long non-coding RNAs (lncRNAs), and 1675 messenger RNAs (mRNAs) differentially expressed through microarray analysis. Second, we constructed ceRNA networks among lncRNAs/circRNAs, miRNAs and mRNAs and identified two ceRNA networks (lncMelttl16/miR-382-5p/Hsd17b7 and circIqch/miR-181d-5p/Stat1) after real time-quantitative polymerase chain reaction (RT-qPCR) validation. Furthermore, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, ncRNAs were found to be involved in biological processes and signaling pathways related to pulmonary fibrosis. KEGG analysis showed that NiONPs activated the Wnt/beta-catenin pathway in rats. In vitro, HFL1 cells were treated with 0, 50, 100, and 200 mug/mL NiONPs for 24 h. We found that NiONPs induced collagen deposition and Wnt/beta-catenin pathway activation. Moreover, a blockade of Wnt/beta-catenin pathway alleviated NiONP-induced collagen deposition. In conclusion, these observations suggested that ncRNAs were crucial in pulmonary fibrosis development and that the Wnt/beta-catenin pathway mediated the deposition of collagen. CI - (c) 2024 Wiley Periodicals LLC. FAU - Liu, Han AU - Liu H AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. FAU - Yang, Mengmeng AU - Yang M AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. FAU - Li, Kun AU - Li K AUID- ORCID: 0000-0003-4374-7705 AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. FAU - Gao, Qing AU - Gao Q AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. FAU - Zheng, Jinfa AU - Zheng J AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. FAU - Gong, Xuefeng AU - Gong X AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. FAU - Wang, Hui AU - Wang H AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. FAU - Sun, Yingbiao AU - Sun Y AUID- ORCID: 0000-0003-3711-8486 AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. FAU - Chang, Xuhong AU - Chang X AUID- ORCID: 0000-0002-5313-0576 AD - Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China. LA - eng GR - 81602874/National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ GR - 31872757/National Natural Science Foundation of China/ GR - 2022-rc-5/Science and Technology Plan Project of Chengguan District in Lanzhou/ GR - 2023-2-9/Science and Technology Plan Project in Lanzhou/ PT - Journal Article DEP - 20240102 PL - United States TA - Environ Toxicol JT - Environmental toxicology JID - 100885357 RN - 0 (beta Catenin) RN - C3574QBZ3Y (nickel monoxide) RN - 0 (RNA, Circular) RN - 0 (RNA, Long Noncoding) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 9007-34-5 (Collagen) RN - 7OV03QG267 (Nickel) SB - IM MH - Male MH - Rats MH - Animals MH - beta Catenin/metabolism MH - RNA, Circular MH - *RNA, Long Noncoding/genetics/metabolism MH - *Pulmonary Fibrosis/chemically induced/genetics MH - Rats, Wistar MH - *MicroRNAs/genetics/metabolism MH - RNA, Messenger/metabolism MH - Gene Expression Profiling MH - Wnt Signaling Pathway/genetics MH - *Nanoparticles/toxicity MH - Collagen MH - Gene Regulatory Networks MH - *Nickel OTO - NOTNLM OT - NiONPs OT - Wnt/beta-catenin OT - ceRNA network OT - noncoding RNA OT - pulmonary fibrosis EDAT- 2024/01/02 11:44 MHDA- 2024/03/11 06:42 CRDT- 2024/01/02 08:00 PHST- 2023/10/15 00:00 [revised] PHST- 2022/07/11 00:00 [received] PHST- 2023/12/01 00:00 [accepted] PHST- 2024/03/11 06:42 [medline] PHST- 2024/01/02 11:44 [pubmed] PHST- 2024/01/02 08:00 [entrez] AID - 10.1002/tox.24088 [doi] PST - ppublish SO - Environ Toxicol. 2024 Apr;39(4):2374-2389. doi: 10.1002/tox.24088. Epub 2024 Jan 2.