Angiotensin II regulates insulin-like growth factor I gene expression in vascular smooth muscle cells.
The potent vasoconstrictor peptide angiotensin II (ang II) has been shown to promote growth of vascular smooth muscle cells (VSMC) in vitro and in vivo. We have previously demonstrated that VSMC synthesize insulin-like growth factor I (IGF I), an important autocrine/paracrine growth factor. Exposure of quiescent VSMC to ang II caused a marked increase in IGF I mRNA levels, peaking at 6 h (199 +/- 26% above control) and sustained for at least 24 h. This increase was completely inhibited by actinomycin D. Nuclear run-on assays indicated that ang II stimulated IGF I gene transcription 3.6-fold. Protein synthesis inhibition with cycloheximide increased basal IGF I mRNA levels but blocked ang II-induced IGF I expression. Immunoreactive IGF I levels in VSMC-conditioned medium were increased by 2.7-fold 24 h following ang II exposure. Measurements of [3H]thymidine incorporation showed that ang II caused a 117% increase in DNA synthesis at 24 h that was almost completely inhibited in the presence of an anti-IGF I antibody. Thus, ang II regulates transcription of the IGF I gene in VSMC and IGF I is required for ang II-induced DNA synthesis. These findings suggest a potentially important role for IGF I as a mediator of the vascular growth responses induced by activation of the renin-angiotensin system in vivo.
Delafontaine
P
P
Department of Medicine, Emory University, Atlanta, Georgia 30322.
Lou
H
H
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic
D012333:RNA, Messenger; D000804:Angiotensin II; D003609:Dactinomycin; D007334:Insulin-Like Growth Factor I; D004247:DNA; D003513:Cycloheximide