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• W4226142445 abstract "Although hypoxia induces aberrant gene expression and dedifferentiation of smooth muscle cells (SMCs), mechanisms that alter dedifferentiation gene expression by hypoxia remain unclear. Therefore, we aimed to gain insight into the hypoxia-controlled gene expression in SMCs. We conducted studies using SMCs cultured in 3% oxygen (hypoxia) and the lungs of mice exposed to 10% oxygen (hypoxia). Our results suggest hypoxia upregulated expression of transcription factor CP2-like protein1, krüppel-like factor 4, and E2f transcription factor 1 enriched genes including basonuclin 2 (Bcn2), serum response factor (Srf), polycomb 3 (Cbx8), homeobox D9 (Hoxd9), lysine demethylase 1A (Kdm1a), etc. Additionally, we found that silencing glucose-6-phosphate dehydrogenase (G6PD) expression and inhibiting G6PD activity downregulated Srf transcript and hypomethylation of SMC genes (Myocd, Myh11, and Cnn1) and concomitantly increased their expression in the lungs of hypoxic mice. Furthermore, G6PD inhibition hypomethylated MEG3, a long non-coding RNA, gene and upregulated MEG3 expression in the lungs of hypoxic mice and in hypoxic SMCs. Silencing MEG3 expression in SMC mitigated the hypoxia-induced transcription of SRF. These findings collectively demonstrate that MEG3 and G6PD codependently regulate Srf expression in hypoxic SMCs. Moreover, G6PD inhibition upregulated SRF-MYOCD-driven gene expression, determinant of a differentiated SMC phenotype." @default.
• W4226142445 created "2022-05-05" @default.
• W4226142445 creator A5025647956 @default.
• W4226142445 creator A5033512267 @default.
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• W4226142445 date "2022-01-01" @default.
• W4226142445 modified "2023-09-26" @default.
• W4226142445 title "Glucose-6-phosphate dehydrogenase and MEG3 controls hypoxia-induced expression of serum response factor (SRF) and SRF-dependent genes in pulmonary smooth muscle cell" @default.
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• W4226142445 doi "https://doi.org/10.1540/jsmr.58.34" @default.
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