TGF-beta 1 potentiates growth factor-stimulated proliferation of vascular smooth muscle cells in genetic hypertension.
We have examined the interactions between transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), or platelet-derived growth factor (PDGF) isoforms PDGF-AB and PDGF-BB on the proliferation of vascular smooth muscle cells isolated from the spontaneously hypertensive rat. TGF-beta 1 alone stimulated [3H]thymidine incorporation approximately twofold without a corresponding increase in cell number. In combination, TGF-beta 1 action was synergistic in further stimulating both DNA synthesis and cell proliferation 100-300% above the responses elicited by each growth factor. To gain further insight into the mechanism responsible for this potentiation, we examined the interaction between TGF-beta 1 and EGF. The synergistic interaction between TGF-beta 1 and EGF on DNA synthesis was independent of initial cell density. This effect of TGF-beta 1 was initiated early in the G1 phase of the cell cycle and did not appear to be mediated through the mobilization of Ca2+ or alterations in c-jun mRNA expression. However, in the presence of both TGF-beta 1 and EGF, there was a sustained elevation of c-myc mRNA levels over a 24-h period. These results suggest that TGF-beta 1 may interact with other growth factors in vivo to enhance their proliferative action on vascular smooth muscle of spontaneously hypertensive rats via mechanisms dependent on c-myc mRNA expression.
Saltis
J
J
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
Agrotis
A
A
Bobik
A
A
D000818:Animals; D002450:Cell Communication; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006133:Growth Substances / Q000494:pharmacology*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D006133:Growth Substances; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA