PMID- 1514589 OWN - NLM STAT- MEDLINE DCOM- 19920925 LR - 20171213 IS - 0002-9513 (Print) IS - 0002-9513 (Linking) VI - 263 IP - 2 Pt 1 DP - 1992 Aug TI - TGF-beta 1 potentiates growth factor-stimulated proliferation of vascular smooth muscle cells in genetic hypertension. PG - C420-8 AB - 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. FAU - Saltis, J AU - Saltis J AD - Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia. FAU - Agrotis, A AU - Agrotis A FAU - Bobik, A AU - Bobik A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Physiol JT - The American journal of physiology JID - 0370511 RN - 0 (Growth Substances) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Cell Communication MH - Cell Cycle/drug effects MH - Cell Division/drug effects MH - DNA/biosynthesis MH - Growth Substances/*pharmacology MH - Hypertension/genetics/metabolism/*pathology MH - Male MH - Muscle, Smooth, Vascular/drug effects/metabolism/*pathology MH - Proto-Oncogene Proteins c-myc/genetics MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Inbred SHR MH - Signal Transduction MH - Transforming Growth Factor beta/*pharmacology EDAT- 1992/08/01 00:00 MHDA- 1992/08/01 00:01 CRDT- 1992/08/01 00:00 PHST- 1992/08/01 00:00 [pubmed] PHST- 1992/08/01 00:01 [medline] PHST- 1992/08/01 00:00 [entrez] AID - 10.1152/ajpcell.1992.263.2.C420 [doi] PST - ppublish SO - Am J Physiol. 1992 Aug;263(2 Pt 1):C420-8. doi: 10.1152/ajpcell.1992.263.2.C420.