Down-regulation of endothelin receptors by transforming growth factor β1 in hepatic stellate cells

Neutralization of transforming growth factor-β attenuates hypertension and prevents renal injury in uremic rats

“…This effect appears to be specific to TGF-b neutralization since ET B receptor downregulation in uremic rats was unaffected by AT 1 blockade with losartan. The improvement of ET B receptor expression with the 1D11 antibody is consistent with the recent observation that TGF-b1 can reduce the ET B receptor expression in cultured hepatic stellate cells [34]. Thus, the increase in TGF-b1 production in uremic animals may play a role in the reduction of vascular and renal ET B receptor expression.…”

Differential effects of TGF-β on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes

“…It was recently demonstrated that ET-1 stimulates fibrogenic gene expression in primary cultured HSC but not in HSC at higher passage numbers [41]. On the other side, TGF-b1 itself reduces ET-1 receptor density in HSC [42]. Therefore, it is reasonable to speculate that the observed zero net effect on CTGF/CCN2 expression upon TGF-b1 stimulation described in this study might be the result of a direct enhancing effect on CTGF/CCN2 expression by TGFb1 that is counteracted by a reduction of CTGF/CCN2 expression due to downregulation of ET-1 receptors.…”

Therapeutic potential of TGF-β inhibition in chronic renal failure

“…TGF-β1 stimulated the expression of the mRNA of the vasocostrictor peptide ET-1 in vascular endothelial cells [112] and reduced ET B receptor expression [113]. In vivo neutralisation of TGF-β1 attenuated hypertension and prevented the reduction of ET B receptor expression in uremic rats with renal mass reduction [108].…”