gms | German Medical Science

Angiotensin-(1-7) was recently found to be an endogenous ligand for the G protein-coupled receptor Mas. Unclear factors of activiated T cells (NFAT) is a ubiquous transcription factor which plays an important role in cardiovascular and skeletal muscle development. The aim of our study is to investigate the signaling pathway between Ang-(1-7)/Mas axis and NFAT. HEK293 cells were transiently transfected by pcDNA3.1RNMas and pNFAT-TA -Luc alone or in combination and the transfected cells were maintained in serum-free DMEM (Dulbecco's Modified Eagle Medium). The luciferase product was measured 24h after transfection. In Mas-transfected cells, the lucifersase activity (fold to control) dose-dependently increased with an increasing amount of Mas (5-100ng), and A-779 (10-6M), a specific antagonist of Ang-(1-7), had no blocking effect on the increased activation of NFAT induced by Mas. In none-Mas transfected cells, the luciferase activity was increased with the increase of Ang-(1-7) (10-11 to 10-5M), and A-779 (10-6M), Irbersatan (an antagonist of Ang II receptor type 1, AT1, 10-6M), PD123319 (an antagonist of Ang II receptor type 2, AT2, 10-6M),and HOE140 (an antagonist of Bradykinin B2 recepotor type 2, B2, 10-6M) could not block the increased activation of NFAT induced by Ang-(1-7). The data showed that Mas constitutively activiate NFAT, and Ang-(1-7) could increase the activation of NFAT via a Mas, AT1, AT2 and B2 independent receptor.