Hepatocyte growth factor (HGF) plays a role in development and regeneration of a variety of tissues, whereas, regulatory mechanisms for HGF expression have been not fully understood. We here found that hydrocortisone potentiate HGF expression in vascular endothelial cells. In rat aortic endothelial cells in culture, hydrocortisone alone had no stimulatory effect on HGF production, whereas it largely potentiates the enhancement of HGF production by dibutyryl cyclic AMP (dbcAMP). Likewise, hydrocortisone markedly potentiated the stimulatory effect of phorbol 12-myristate 13-acetate on HGF production in human umbilical vein and pulmonary artery endothelial cells. Hydrocortisone alone did not induce HGF mRNA expression, whereas it augmented HGF mRNA expression induced by dbcAMP in rat aortic endothelial cells, suggesting that the potentiation by hydrocortisone was attributable to transcriptional regulation of HGF gene. In contrast, transforming growth factor-β1, endothelin-1, and nitric oxide suppressed HGF expression in endothelial cells. Previous studies demonstrated that hydrocortisone suppresses HGF expression in non-endothelial cells. Taken together, hydrocortisone bi-directionally regulates HGF expression in cell type-dependent manner and our results provide a unique regulatory mechanism for HGF expression in vascular endothelial cells.
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