TGF-beta promotes proliferation of cultured SMC via both PDGF-AA-dependent and PDGF-AA-independent mechanisms.
TGF-beta promotes proliferation of cultured SMC via both PDGF-AA-dependent and PDGF-AA-independent mechanisms.
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DOI：
10.1172/jci117199
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发表时间：
1994-05
期刊：
影响因子：
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通讯作者：
G. Stouffer;G. Owens
中科院分区：
文献类型：
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作者：
G. Stouffer;G. Owens
转化生长因子- β 1 （tgf - β 1）参与血管损伤后平滑肌细胞（SMC）的生长。对tgf - β诱导培养SMC生长的研究发现，只有适度的有丝分裂作用，主要依赖于血小板衍生生长因子- aa （PDGF-AA）的自分泌。然而，最近的研究表明，tgf - β也可能具有独立于PDGF-AA的延迟生长作用。本研究的目的是研究tgf - β对培养SMC的慢性生长反应的影响。结果表明，tgf - β引发了延迟的生长反应（3H-TdR增加24倍）。PDGF-AA的生成在24 h时增加了8倍。然而，PDGF-AA的中和抗体仅抑制10-40%的延迟tgf - β诱导的生长。与tgf - β共同处理可延迟表皮生长因子(EGF)-、碱性成纤维细胞生长因子(bFGF)-或pdgf - bb -诱导的进入S期，但对这些生长因子的延迟生长反应分别提高了16.0倍、5.8倍或4.2倍。PDGF-AA的中和抗体对这些协同反应没有影响，外源性PDGF-AA不会增加对EGF、bFGF或PDGF-BB的生长反应。总之，tgf - β单独或与EGF、bFGF或PDGF-BB联合诱导显著的延迟生长反应，这些反应在很大程度上不依赖于PDGF-AA。
Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in mediating smooth muscle cell (SMC) growth after vascular injury. Studies examining TGF-beta-induced growth of cultured SMC have identified only modest mitogenic effects which are largely dependent on autocrine production of platelet-derived growth factor-AA (PDGF-AA). Recent studies have suggested, however, that TGF-beta also may have delayed growth effects independent of PDGF-AA. The aims of the present studies were to examine the effects of TGF-beta on chronic growth responses of cultured SMC. Results demonstrated that TGF-beta elicited a delayed growth response (24 fold increase in 3H-TdR incorp. from 48-72 h) and enhanced SMC production of PDGF-AA (eightfold increase at 24 h). Neutralizing antibodies to PDGF-AA, however, inhibited only 10-40% of delayed TGF-beta-induced growth. Co-treatment with TGF-beta transiently delayed epidermal growth factor (EGF)-, basic fibroblast growth factor (bFGF)-, or PDGF-BB-induced entry into S phase but enhanced the delayed growth responses to these growth factors by 16.0-, 5.8-, or 4.2-fold, respectively. Neutralizing antibodies to PDGF-AA had no effect on these synergistic responses and exogenous PDGF-AA did not increase growth responses to EGF, bFGF, or PDGF-BB. In summary, TGF-beta induces marked delayed growth responses, alone and in combination with EGF, bFGF or PDGF-BB, that are largely independent of PDGF-AA.