Abstract
The present study was undertaken to determine whether transforming growth factor (TGF)-β1 modulates the cellular actions of arginine vasopressin (AVP) in cultured rat glomerular mesangial cells. AVP increased cytosolic free calcium ([Ca2+]i), and TGF-β1 dose-dependently reduced the AVP-mobilized [Ca2+]i. Such an inhibition by exogenous TGF-β1 was abolished by liposomal transfection of antisense oligodeoxynucleotide for the TGF-β type II receptor. AVP activated mitogen-activated protein (MAP) kinase, which was significantly reduced by 1ng/ml TGF-β1. AVP increased [3H] thymidine incorporation into mesangial cells in a dose-dependent manner, and 1ng/ml TGF-β1 significantly reduced the AVP-stimulated [3H] thymidine incorporation. However, 10μM antisense oligodeoxynucleotide for the TGF-β type II receptor seemed to attenuate the inhibition by TGF-β1. 1×10-7M AVP significantly increased inositol 1, 4, 5-trisphosphate (IP3) production by 1.8-fold, but this production was totally blunted by 1ng/ml TGF-β1. TGF-β1 did not affect [3H] AVP receptor binding. 1×10-6M AVP concentration stimulated TGF-β1 production in mesangial cells by 4-fold. These results indicate that TGF-β1 inhibits the cellular signaling of AVP at steps beyond the AVP receptors and prior to the phospholipase C activation, and that TGF-β1 may participate in a negative feedback regulation on the cellular action of AVP in glomerular mesangial cells. (Hypertens Res 1999; 22: 173-180)
