High glucose promotes connective tissue growth factor expression in vascular endothelial cells with TGFβ-dependent pathways

Objective Vascular endothelial dysfunction is characterized by multiple interactions between endothelial cells and components of the blood.This study was designed to study the effect of high glucose on pro-atherogenic connective tissue growth factor(CTGF) in vascular endothelial cells.Methods Cultured human umbilical vein endothelial cells(HUVECs) were treated with normal glucose(5.5 mM),high glucose(25 mM),25mM mannitol or high glucose together with a neutralizing antibody to transforming growth factor β1(TGF-β1) for 24,48 or 72 hours respectively.The expression of CTGF mRNA and protein was determined with RT-PCR and western Blot,respectively.Results Expression of CTGF mRNA was up-regulated 24 hour after exposed to high glucose condition,which remained the elevated level up to 48 hours.Meanwhile,CTGF protein level increased after high glucose exposure for 24 hours,and maintained elevated status up to 48 hours.The upregulation of CTGF appears to be TGFβ-dependent since an anti-TGFβ neutralizing antibody partially blocks the effect of high glucose on CTGF gene and protein expression.Conclusion High glucose-induced CTGF expression in vascular endothelial cells is mediated,at least partially,with the TGF-β-dependent pathways,which suggests that CTGF might be an important factor involved in the patho-physiological responses to high glucose in vascular endothelial cells.