Angiotensin II-stimulated expression of transforming growth factor beta in renal proximal tubular cells: attenuation after stable transfection with the c-mas oncogene.
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.
Wolf
G
G
Department of Medicine, University of Hamburg, Germany.
Ziyadeh
F N
FN
Zahner
G
G
Stahl
R A
RA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta; D000804:Angiotensin II