Angiotensin II regulates human vascular smooth muscle alpha-actin gene expression.
Angiotensin II (AII) has been shown to induce vascular smooth muscle cell (VSMC) hypertrophy and increased expression of vascular cytoskeletal proteins. We have studied basal and AII-induced expression of the chloramphenicol acetyl transferase (CAT) gene driven by three fragments of the human vascular smooth muscle (SM) alpha-actin promoter. We show basal CAT expression driven by the three fragments of the promoter when the constructs are transiently transfected into rat aortic VSMCs. AII in a concentration-dependent manner (1.0 nM to 10 microM) increased expression of the CAT gene driven by 896 bp fragment. When comparing the 896 bp fragment to fragments successively deleted at the 5' end (674 bp and 258 bp respectively), AII markedly stimulated CAT expression driven by the 896 bp fragment (257 +/- 31% over control, p < 0.01), stimulated CAT expression driven by 674 bp fragment to an apparently lesser degree (189 +/- 20% over control, p < 0.01), and tended to stimulate CAT expression driven by the 258 bp fragment, though not significantly greater than baseline (157 +/- 28% of control). These data suggest that AII exerts transcriptional regulation of human SM alpha-actin gene through activation of cis-acting element(s) in an upstream area localized between positions -258 and -896 of the SM alpha-actin promoter. Such findings help establish the role of AII in enhancement of expression of components of the contractile apparatus.
Andrawis
N S
NS
Department of Medicine, Brown University School of Medicine, Providence, RI.
Ruley
E H
EH
Abernethy
D R
DR
D000199:Actins / Q000096:biosynthesis*; D000804:Angiotensin II / Q000187:drug effects*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
D000199:Actins; D011994:Recombinant Proteins; D000804:Angiotensin II; D015500:Chloramphenicol O-Acetyltransferase