circRNAs deregulation in exosomes derived from BEAS-2B cells is associated with vascular stiffness induced by PM2.5

Qingping Liu; Yaling Zhang; Bin Han; Mengruo Wang; Huaifang Hu; Jie Ning; Wentao Hu; Meiyu Chen; Yaxian Pang; Yuanyuan Chen; Lei Bao; Yujie Niu; Rong Zhang

doi:10.1016/j.jes.2023.02.027

circRNAs deregulation in exosomes derived from BEAS-2B cells is associated with vascular stiffness induced by PM_2.5

J Environ Sci (China). 2024 Mar:137:527-539. doi: 10.1016/j.jes.2023.02.027. Epub 2023 Feb 24.

Authors

Qingping Liu¹, Yaling Zhang¹, Bin Han², Mengruo Wang¹, Huaifang Hu¹, Jie Ning¹, Wentao Hu¹, Meiyu Chen¹, Yaxian Pang¹, Yuanyuan Chen³, Lei Bao⁴, Yujie Niu⁵, Rong Zhang⁶

Affiliations

¹ Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, China.
² Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, China; State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China.
⁴ Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang 050017, China.
⁵ Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, China.
⁶ Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: rongzhang@hebmu.edu.cn.

PMID: 37980036
DOI: 10.1016/j.jes.2023.02.027

Abstract

As an environmental pollutant, ambient fine particulate matter (PM_2.5) was linked to cardiovascular diseases. The molecular mechanisms underlying PM_2.5-induced extrapulmonary disease has not been elucidated clearly. In this study the ambient PM_2.5 exposure mice model we established was to explore adverse effects of vessel and potential mechanisms. Long-term PM_2.5 exposure caused reduced lung function and vascular stiffness in mice. And chronic PM_2.5 induced migration and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B cells. After PM_2.5 treatment, the circRNAs and mRNAs levels of exosomes released by BEAS-2B cells were detected by competing endogenous RNA (ceRNA) array, which contained 1664 differentially expressed circRNAs (DE-circRNAs) and 308 differentially expressed mRNAs (DE-mRNAs). By bioinformatics analysis on host genes of DE-circRNAs, vascular diseases and some pathways related to vascular diseases including focal adhesion, tight junction and adherens junction were enriched. Then, ceRNA network was constructed, and DE-mRNAs in ceRNA network were conducted functional enrichment analysis by Ingenuity Pathway Analysis, which indicated that hsa_circ_0012627, hsa_circ_0053261 and hsa_circ_0052810 were related to vascular endothelial dysfunction. Furthermore, it was verified experimentally that Exo^PM2.5 could induce endothelial dysfunction by increased endothelial permeability and decreased relaxation in vitro. In present study, we investigated in-depth knowledge into the molecule events related to PM_2.5 toxicity and pathogenesis of vascular diseases.

Keywords: Endothelial dysfunction; Exosome; Fine particulate matter; Vascular stiffness; ceRNA microarray.

MeSH terms

Animals
Exosomes*
Mice
MicroRNAs*
Particulate Matter / toxicity
RNA, Circular / genetics
Vascular Diseases*
Vascular Stiffness*

Substances

RNA, Circular
Particulate Matter
MicroRNAs