POSSIBLE ROLE OF C-JUN IN TRANSCRIPTION OF THE MOUSE RENIN GENE

Background Renin is a rate-limiting enzyme for activity of the circula ting renin-angiotensin system (RAS) and expression of the renin gene i s regulated by a variety of stimuli. In this study, we examined a poss ible role of c-Jun in the transcription of renin gene. Methods. The re nin promoter, chloramphenicol acetyltransferase (CAT), fusion genes wi th or without c-Jun expression vector (pSV-c-Jun) were transfected int o human embryonic kidney (HEK) cells, and the effects of c-Jun were ex amined by deletion and mutation analyses of CAT assay and by in vitro transcription-primer extension assay. We also examined the effects of c-Jun on DNA-binding activity to the renin promoter by electrophoretic mobility shift assay (EMSA). Furthermore, we examined the effects of c-Jun on transcription of the renin gene in enriched juxtaglomerular ( JG) cells by cotransfection with pSV-c-Jun and by treatment with antis ense c-jun oligodeoxynucleotides. Results. Promoter activity of the re nin gene was increased by c-Jun overexpression in HEK cells, and the p roximal promoter region from -47 to +16 was sufficient for transcripti onal activation by c-Jun. Although mutation of activator protein-1 (AP -1) element-like sequences in the proximal promoter did not affect c-J un-mediated stimulation, mutation of the core promoter including the T ATA box inhibited c-Jun-mediated transcription. The results of EMSA sh owed that c-Jun overexpression produced a binding of nuclear factor, w hich was HEK cell-specific and distinct from TATA box-binding protein and AP-1 family transcription factor, to the renin core promoter regio n (RC element) from -36 to -20. The overexpression of c-Jun activated the renin promoter in renin-expressing JG cells, and antisense c-jun d ecreased the activity of renin promoter and expression of renin mRNA i n JG cells. Conclusions. These results indicate that the RC element pl ays a role in c-Jun-mediated transcriptional regulation of the renin g ene in HEK cells, and suggest that c-Jun participates in the regulatio n of renin gene expression in JG cells of the kidney.