Abstract
Insulin contributes to atherosclerosis, but the potential mechanisms are kept unclear. In this study, insulin promoted proliferation of A7r5 cells. Microarray analysis indicated that insulin significantly changed 812 probe sets of genes, including 405 upregulated and 407 downregulated ones (fold change ≥ 1.5 or ≤ − 1.5; p < 0.05). Gene ontology analysis showed that the differentially expressed genes were involved in a number of processes, including the regulation of cell proliferation/migration/cycle, apoptotic process, oxidative stress, inflammatory response, mitogen-activated protein kinase (MAPK) activity, lipid metabolic process and extracellular matrix organization. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the genes were involved in biosynthesis of amino acids, fatty acid metabolism, glycolysis/gluconeogenesis, metabolic pathways, regulation of autophagy, cell cycle and apoptosis, as well as the PI3K-Akt, MAPK, mTOR and NF-κB signaling pathways. Additionally, insulin enhanced phosphorylation of MAPK kinase 1/2 and Akt, suggesting activation of the MAPK and PI3K-Akt signaling pathways. Inhibition of ERK1/2 reduced insulin-induced proliferation. This study revealed the proliferative effects of insulin and displayed global gene expression profile of A7r5 cells stimulated by insulin, suggesting new insight into the molecular pathogenesis of insulin promoting atherosclerosis.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This study was supported by the National Natural Science Foundation of China (Nos. 81460711 and 81760852), the Guangxi National Natural Science Foundation (Nos. 2017GXNSFAA198284 and 2014GXNSFAA118264), the Innovation Project of Guangxi Graduate Education (No. JGY2018084), the Guangxi Key Laboratory of Chinese Medicine Foundation Research (No. 20-065-53), Guangxi University of Chinese Medicine, the Cultivation Program of 1000 Young and Middle-aged Backbone Teachers in Higher Education of Guangxi (No. Gui Teacher Education [2019]81), and the Guangxi Collabrative Innovation Center for Scientific Achievements Transformation and Application on Traditional Chinese Medicine (No. 05020058).
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Duan, H., Feng, X. & Huang, X. Effects of insulin on the proliferation and global gene expression profile of A7r5 cells. Mol Biol Rep 48, 1205–1215 (2021). https://doi.org/10.1007/s11033-021-06200-8
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DOI: https://doi.org/10.1007/s11033-021-06200-8