Abstract
Curcumin (Cur) has various pharmacological activities, including anti-inflammatory, antiapoptotic and anticancer effects. However, there is no report on the effect of Cur on endothelial cell fibrosis. This study was designed to investigate the effect and mechanism of Cur on endothelial cell fibrosis. An endothelial cell fibrosis model was established by using transforming growth factor (TGF) induction. Proliferation assays, qRT-PCR, western blotting and immunostaining were performed to investigate the effects and mechanism of Cur on endothelial cell fibrosis. We found that in human umbilical vein endothelial cells (HUVECs), TGF-β1 treatment significantly decreased the expression of nuclear factor erythroid-2-related factor 2 (NRF-2), dimethylarginine dimethylaminohydrolase-1 (DDAH1), and VE-cadherin, the secretion of cellular nitric oxide (NO) and the activity of nitrous oxide synthase (NOS), while asymmetric dimethylarginine (ADMA) and the release of inflammatory factors were elevated. Immunofluorescence showed decreased CD31 and increased α-smooth muscle actin (α-SMA). Overexpression of NRF-2 significantly attenuated the effects of TGF-β1, while downregulation of DDAH1 potently counteracted the effect of NRF-2. In addition, ADMA treatment resulted in similar results to those of TGF-β1, and Cur significantly attenuated the effect of TGF-β1, accompanied by increased VE-cadherin, DDAH1 and NRF-2 and decreased matrix metalloproteinase-9 (MMP-9) and extracellular regulated protein kinases 1/2 (ERK1/2) phosphorylation. The NRF-2 inhibitor ML385 had the opposite effect as that of Cur. These results demonstrated that Cur inhibits TGF-β1-induced endothelial-to-mesenchymal transition (EndMT) by stimulating DDAH1 expression via the NRF-2 pathway, thus attenuating endothelial cell fibrosis.