ROLE OF PDGF-A EXPRESSION IN THE CONTROL OF VASCULAR SMOOTH-MUSCLE CELL-GROWTH BY TRANSFORMING GROWTH-FACTOR-BETA

被引:228
作者
MAJACK, RA
MAJESKY, MW
GOODMAN, LV
机构
[1] UPJOHN CO,KALAMAZOO,MI 49001
[2] UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195
关键词
D O I
10.1083/jcb.111.1.239
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Transforming growth factor-β (TGF-β) is a multifunctional regulatory peptide that can inhibit or promote the proliferation of cultured vascular smooth muscle cells (SMCs), depending on cell density (Majack, R. A. 1987. J. Cell Biol 105:465-471). In this study, we have examined the mechanisms underlying the growth-promoting effects of TGF-β in confluent SMC cultures. In mitogenesis assays using confluent cells, TGF-β was found to potentiate the stimulatory effects of serum, PDGF, and basic fibroblast growth factor (bFGF), and was shown to act individually as a mitogen for SMC. In gene and protein expression experiments, TGF-β was found to regulate the expression of PDGF-A and thrombospondin, two potential mediators of SMC proliferative events. The induction of thrombospondin protein and mRNA was density-dependent, delayed relative to its induction by PDGF and, based on cycloheximide experiments, appeared to depend on the de novo synthesis of an intermediary protein (probably PDGF-A). The relationship between PDGF-A expression and TGF-β-mediated mitogenesis was investigated, and it was determined that a PDGF-like activity (probably PDGF-A) was the biological mediator of the growth-stimulatory effects of TGF-β on confluent SMC. The effects of purified homodimers of PDGF-A on SMC replication were investigated, and it was determined that PDGF-AA was mitogenic for cultured SMC, particularly when used in combination with other growth factors such as bFGF and PDGF-BB. The data suggest several molecular mechanisms that may account for the ability of TGF-β to promote the growth of confluent SMC in culture.
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页码:239 / 247
页数:9
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