Role of transforming growth factor-beta 1 in the cellular growth response to angiotensin II.
We have shown that angiotensin II (Ang II)-induced hypertrophy of vascular smooth muscle cells is dependent on the balance between proliferative and antiproliferative growth factors, specifically basic fibroblast growth factor and transforming growth factor-beta 1 (TGF-beta 1), respectively. We now present evidence, based on two phenotypically distinct cell cultures, that the ability to secrete the biologically active form of TGF-beta 1 is central to the growth response to Ang II. Two separate cultures were examined, one in which Ang II induces hypertrophy and the other in which Ang II induces hyperplasia. Ang II induces the expression of basic fibroblast growth factor twofold to fivefold in both cultures. Furthermore, both cultures express TGF-beta 1. In the culture that responds with hypertrophy, Ang II induces the expression of the active form of TGF-beta 1 twofold to threefold. However, in the culture that responds with hyperplasia, no active TGF-beta 1 was detected either at baseline or after Ang II exposure. Interestingly, all the TGF-beta 1 present was in the inactive, latent form. In the culture that responded with hyperplasia, Ang II induced a fourfold to fivefold increase in DNA synthesis. This increase could be abolished by the addition of active TGF-beta 1. Thus in these two cultures the ability to activate TGF-beta 1 dictates the cellular response to Ang II. These results support our hypothesis that a balance of proliferative and antiproliferative autocrine signals mediates the growth control of vascular smooth muscle cells.
Falk Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA 94305-5246.
Y
Y
Koibuchi
W S
WS
Lee
G H
GH
Gibbons
R E
RE
Pratt
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006965:Hyperplasia; D006984:Hypertrophy; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D004247:DNA