Inhibition by transforming growth factor-beta1 of the cellular action of arginine vasopressin in cultured rat glomerular mesangial cells.
The present study was undertaken to determine whether transforming growth factor (TGF)-beta1 modulates the cellular actions of arginine vasopressin (AVP) in cultured rat glomerular mesangial cells. AVP increased cytosolic free calcium ([Ca2+]i), and TGF-beta1 dose-dependently reduced the AVP-mobilized [Ca2+]i. Such an inhibition by exogenous TGF-beta1 was abolished by liposomal transfection of antisense oligodeoxynucleotide for the TGF-beta type II receptor. AVP activated mitogen-activated protein (MAP) kinase, which was significantly reduced by 1 ng/ml TGF-beta1. AVP increased [3H]thymidine incorporation into mesangial cells in a dose-dependent manner, and 1 ng/ml TGF-beta1 significantly reduced the AVP-stimulated [3H]thymidine incorporation. However, 10 microM antisense oligodeoxynucleotide for the TGF-beta type II receptor seemed to attenuate the inhibition by TGF-beta1. 1 X 10(-7) M AVP significantly increased inositol 1,4,5-trisphosphate (IP3) production by 1.8-fold, but this production was totally blunted by 1 ng/ml TGF-beta1. TGF-beta1 did not affect [3H]AVP receptor binding. 1 X 10(-6) M AVP concentration stimulated TGF-beta1 production in mesangial cells by 4-fold. These results indicate that TGF-beta1 inhibits the cellular signaling of AVP at steps beyond the AVP receptors and prior to the phospholipase C activation, and that TGF-beta1 may participate in a negative feedback regulation on the cellular action of AVP in glomerular mesangial cells.
Higashiyama
M
M
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Ishikawa
S
S
Saito
T
T
Nakamura
T
T
Kusaka
I
I
Nagasaka
S
S
Honda
K
K
Saito
T
T
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012076:Renal Agents / Q000378:metabolism / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D018125:Receptors, Transforming Growth Factor beta; D012076:Renal Agents; D016212:Transforming Growth Factor beta; D001127:Arginine Vasopressin; D002118:Calcium