Inhibitors of oxygen sensing prolyl hydroxylases regulate nuclear localization of the transcription factors Smad2 and YAP/TAZ involved in CTGF synthesis
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- 作者：Felix Preissera ; Klaudia Giehlb ; Margot Rehma ; Margarete Goppelt-Struebea ; margarete.goppelt-struebe@uk-erlangen.de" class="auth_mail" title="E-mail the corresponding author
- 关键词：CTGF ; connective tissue growth factor ; DMOG ; dimethyloxalyl glycine ; HIF ; hypoxia inducible transcription factor ; HRE ; HIF responsive element ; PHD ; prolyl hydroxylase domain enzymes ; TAZ ; transcription co-activator with PDZ-binding motif ; TGFβ ; transforming growth factor β ; YAP ; Yes associated protein
- 刊名：Biochimica et Biophysica Acta (BBA)-Molecular Cell Research
- 出版年：2016
- 出版时间：August 2016
- 年：2016
- 卷：1863
- 期：8
- 页码：2027-2036
- 全文大小：1107 K
文摘
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In human primary tubular epithelial cells, inhibition of HIF sensing prolylhydroxylases (PHD) by DMOG or exposure of the cells to hypoxia upregulated Smad3 expression.
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Inhibition of HIF sensing prolylhydroxylases (PHD) by DMOG or hypoxia upregulated Smad3 expression.
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By contrast, nuclear localization of Smad2 was reduced in TGFβ-1-stimulated primary tubular epithelial cells.
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Changes in nuclear Smad2 correlated with a reduced expression of the pro-fibrotic factor CTGF.
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Inhibition of PHD also partially reduced nuclear localization of transcription factors YAP and TAZ.
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These data highlight a novel mechanism of negative regulation of gene expression by PHD inhibition or hypoxia.