Transcriptional regulation of adrenomedullin in rat vascular smooth muscle cells.
Adrenomedullin (AM), a potent vasorelaxant peptide recently identified in extracts of pheochromocytoma, is actively secreted from vascular smooth muscle cells (VSMC). AM production in rat VSMC is potently stimulated by proinflammatory cytokines including TNF alpha, and glucocorticoids and many vasoactive substances have also been shown to alter AM synthesis. To study AM promoter function, we cloned the 5'-flanking region of the rat AM gene, and AM promoter function was assessed in rat VSMC stably transfected with a construct containing the cloned fragment. This 1.4 kb AM promoter region includes a number of putative transcriptional control elements. The promoter activity in VSMC was stimulated by TNF alpha and dexamethasone, and was suppressed by 8-bromo-cAMP and forskolin. These data indicate that transcriptional regulation is an important mechanism for AM production in VSMC.
Hattori
Y
Y
Department of Endocrinology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. yhattori@dokkyomed.ac.jp
Mimura
A
A
Akimoto
K
K
Kasai
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D053607:Adrenomedullin; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018387:Codon, Initiator / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D020218:Response Elements / Q000235:genetics; D016385:TATA Box / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016375:Antisense Elements (Genetics); D018387:Codon, Initiator; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D053607:Adrenomedullin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003907:Dexamethasone; D000469:Alkaline Phosphatase