Angiotensin II-stimulated expression of transforming growth factor beta in renal proximal tubular cells: attenuation after stable transfection with the c-mas oncogene.

Abstract

Angiotensin II (Ang II) stimulates cellular hypertrophy of cultured murine proximal tubular cells (MCT cells). This Ang II-mediated hypertrophy depends on the endogenous induction and autocrine action of transforming growth factor-beta (TGF-beta). We have previously demonstrated that permanent transfection of MCT cells with the c-mas oncogene, whose protein product encodes a serpentine receptor-like moiety coupled to G proteins without an hitherto identified ligand, changes the hypertrophic actions of Ang II into a proliferative response (Am J Physiol 263: F931-F938, 1992). The present study demonstrated that Ang II failed to stimulate induction of TGF-beta 1 protein in c-mas transfected MCT cells under the control of SV 40 promoter/enhancer (pSV2mas) as measured by mink cell bioassay and specific ELISA for TGF-beta 1. Moreover, in contrast to either wild-type MCT cells or to cells permanently transfected with the SV 40 based expression plasmid only (pSV2 cells), Ang II stimulated gene transcription and mRNA expression of TGF-beta 1 were decreased in c-mas transfected cells. Our findings demonstrate that the Ang II-induced proliferation of c-mas transfected MCT cells most likely depends on failure of TGF-beta 1 induction in these cells. c-mas transfected cells are a useful tool to further investigate the complex relationships between activation of second messengers subsequent to binding of Ang II to AT1-receptors and gene regulation like transcription of TGF-beta 1.