Transcriptomic‐based toxicological investigations of ethanol to human umbilical vein endothelial cells

Abstract

Ethanol has a complex effect on the cardiovascular system in humans, but the systemic effects of ethanol to endothelial cells were rarely investigated. In this study, we exposed human umbilical vein endothelial cells (HUVECs) to 5‐ or 50‐mM ethanol and performed transcriptomics to investigate the systemic effects of ethanol. While these concentrations of ethanol did not significantly affect HUVEC viability, 5‐mM ethanol significantly upregulated and downregulated 59 and 73 genes, respectively, whereas 50‐mM ethanol significantly upregulated and downregulated 50 and 80 genes, respectively. Totally, 37 genes were shared by the two concentrations of ethanol. The most significantly altered gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway after 5‐mM ethanol treatment were nucleic acid binding (GO:0003676) and Herpes simplex virus 1 infection (ko05168), respectively, whereas the most significantly altered GO term and KEGG pathway by 50‐mM ethanol treatment were aryl sulfotransferase activity (GO:0004062) and chemical carcinogenesis (ko05204). We further verified that ethanol treatment downregulated the mRNA levels of CD38 molecule (CD38), ORAI calcium release‐activated calcium modulator 2 (ORAI2), cysteinyl leukotriene receptor 2 (CYSLTR2), key genes involved in calcium signaling pathway (ko04020), as well as integrin subunit alpha 2 (ITGA2), and cAMP responsive element binding protein 3 like 2 (CREB3L2), key genes involved in PI3K‐Akt signaling pathway (ko04151). The results from this study suggested that ethanol could induce systemic effects and alter signaling pathways in HUVECs.

Chronic Alcohol Reduces Bone Formation Through Inhibiting Proliferation and Promoting Aging of Endothelial Cells in Type-H Vessels

“…We found that high concentration of alcohol could promote the senescence of endothelial cells, and the aging endothelial cells would further affect the osteogenic differentiation of BM-MSCs, which may provide a new therapeutic target for aging osteoporosis. Previous studies found that through the inhibition of PI3K-Akt signaling pathway, high concentration of alcohol may alter many signaling pathways in HUVECs [34]. This suggests the effects of alcohol on cell proliferation, differentiation, apoptosis and migration.…”

Non-canonical Endoplasmic Reticulum Stress Transducers CREB3 family in cancer and other diseases

“…In addition to T cells, CREB3L1 and CREB3L2 are also functionally involved in the transdifferentiation of hepatic stellate cells (HSCs) and impacts the progression of liver fibrosis 36,63 . Interestingly, CREB3L2 appears to be elevated upon alcohol intake, suggesting additional potential functions of CREB3L2 in alcohol metabolism and even the pathological conditions caused by alcohol abuse [64][65][66] .…”

Introduction to special issue endothelial cells in toxicology: Current status and future perspectives

“…The authors showed that ethanol changed global gene expression profiles, gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. At low level of ethanol treatment (5 mM), key genes involved in calcium signaling pathway (ko04020) were altered, whereas at high level of ethanol treatment (50 mM), key genes involved in PI3K‐Akt signaling pathway (ko04151) were altered (Liu et al, 2020). Cheng et al showed that zirconia NPs with or without the presence of free fatty acids (FFAs) did not significantly induce cytotoxicity or lipid accumulation in HUVECs.…”