In human primary tubular epithelial cells, inhibition of HIF sensing prolylhydroxylases (PHD) by DMOG or exposure of the cells to hypoxia upregulated Smad3 expression.
Inhibition of HIF sensing prolylhydroxylases (PHD) by DMOG or hypoxia upregulated Smad3 expression.
By contrast, nuclear localization of Smad2 was reduced in TGFβ-1-stimulated primary tubular epithelial cells.
Changes in nuclear Smad2 correlated with a reduced expression of the pro-fibrotic factor CTGF.
Inhibition of PHD also partially reduced nuclear localization of transcription factors YAP and TAZ.
These data highlight a novel mechanism of negative regulation of gene expression by PHD inhibition or hypoxia.