Effects of PM2.5 exposure on clock gene BMAL1 and cell cycle in human umbilical vein endothelial cells

Haochong Shen; Meidi Gong; Minghao Zhang; Shikun Sun; Rao Zheng; Qing Yan; Juan Hu; Xiaobin Xie; Yan Wu; Junjie Yang; Jing Wu; Jing Yang

doi:10.1093/toxres/tfae022

Effects of PM_2.5 exposure on clock gene BMAL1 and cell cycle in human umbilical vein endothelial cells

Toxicol Res (Camb). 2024 Feb 26;13(1):tfae022. doi: 10.1093/toxres/tfae022. eCollection 2024 Feb.

Authors

Haochong Shen¹, Meidi Gong¹, Minghao Zhang¹, Shikun Sun¹, Rao Zheng¹, Qing Yan¹, Juan Hu¹, Xiaobin Xie¹, Yan Wu¹, Junjie Yang¹, Jing Wu¹, Jing Yang²

Affiliations

¹ Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
² School of Basic Medicine and Forensic Medicine, Baotou Medical College, Inner Mongolia University of Science and Technology, 31 Jianshe Road, Donghe District, Baotou, Inner Mongolia 014040, China.

PMID: 38419835
PMCID: PMC10898333 (available on 2025-02-26)
DOI: 10.1093/toxres/tfae022

Abstract

Background: Fine particulate matter (PM_2.5) exposure has been closely associated with cardiovascular diseases, which are relevant to cell cycle arrest. Brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) not only participates in regulating the circadian clock but also plays a role in modulating cell cycle. However, the precise contribution of the circadian clock gene BMAL1 to PM_2.5-induced cell cycle change remains unclear. This study aims to explore the impact of PM_2.5 exposure on BMAL1 expression and the cell cycle in human umbilical vein endothelial cells (HUVECs).

Methods: HUVECs was exposed to PM_2.5 for 24 hours at different concentrations ((0, 12.5, 25, 75 and 100 μg.mL-1) to elucidate the potential toxic mechanism. Following exposure to PM_2.5, cell viability, ROS, cell cycle, and the expression of key genes and proteins were detected.

Results: A remarkable decrease in cell viability is observed in the PM_2.5-exposed HUVECs, as well as a significant increase in ROS production. In addition, PM_2.5-exposed HUVECs have cycle arrest in G0/G1 phase, and the gene expression of p27 is also markedly increased. The protein expression of BMAL1 and the gene expression of BMAL1 are increased significantly. Moreover, the protein expressions of p-p38 MAPK and p-ERK1/2 exhibit a marked increase in the PM_2.5-exposed HUVECs. Furthermore, following the transfection of HUVECs with siBMAL1 to suppress BMAL1 expression, we observed a reduction in both the protein and gene expression of the MAPK/ERK pathway in HUVECs exposed to PM_2.5.

Conclusions: Overall, our results indicate that PM_2.5 exposure significantly upregulates the circadian clock gene expression of BMAL1 and regulates G0/G1 cell cycle arrest in HUVECs through the MAPK/ERK pathway, which may provide new insights into the potential molecular mechanism regarding BMAL1 on PM_2.5-induced cardiovascular diseases.

Keywords: BMAL1; HUVECs; MAPK/ERK; PM2.5; cell cycle.