Janat M F, Liau G
Laboratory of Molecular Biology, American Red Cross, Jerome H. Holland Laboratory for Biomedical Sciences, Rockville, Maryland 20855.
J Cell Physiol. 1992 Feb;150(2):232-42. doi: 10.1002/jcp.1041500203.
We have studied the effect of transforming growth factor beta 1 (TGF-beta 1) on vascular smooth muscle cell (SMC) mitogenesis and expression of thrombospondin and other growth related genes. We found that TGF-beta 1 treatment of vascular SMC induced a prolonged increase in steady-state mRNA levels of thrombospondin as well as alpha 1 (IV) collagen. The increase began at approximately 2 h, peaked by 24 h, and remained considerably elevated 48 h after growth factor addition. There was a corresponding increase in thrombospondin protein as well as increased expression of several other secreted polypeptides. The increase in thrombospondin contrasted sharply with that observed for platelet-derived growth factor (PDGF) which induced a rapid and transient increase in thrombospondin mRNA level. Although TGF-beta 1 was able to directly enhance expression of thrombospondin as well as the growth-related genes c-fos and c-myc, and induced c-fos expression with identical kinetics as PDGF, it was unable to elicit [3H]thymidine incorporation into DNA in three independent smooth muscle cell strains. However, TGF-beta 1 was able to strongly increase the mitogenic response of SMC to PDGF. Addition of both TGF-beta 1 and PDGF to SMC also caused a synergistic increase in the expression of thrombospondin as well as c-myc. Interestingly, in one other smooth muscle cell strain, a weak and delayed mitogenic response to TGF-beta 1 alone was observed. Our results strongly suggest that induction of thrombospondin expression by TGF-beta 1 and by PDGF occurs by distinct mechanisms. In addition, that TGF-beta 1 can enhance PDGF-induced mitogenesis may be due to the ability of TGF-beta 1 to directly induce the expression of thrombospondin, c-fos, c-myc, and the PDGF beta-receptor.
我们研究了转化生长因子β1（TGF-β1）对血管平滑肌细胞（SMC）有丝分裂以及血小板反应蛋白和其他生长相关基因表达的影响。我们发现，用TGF-β1处理血管SMC可导致血小板反应蛋白以及α1（IV）型胶原的稳态mRNA水平长时间升高。这种升高在大约2小时开始，24小时达到峰值，并在添加生长因子后48小时仍显著升高。血小板反应蛋白的蛋白质水平相应增加，同时其他几种分泌多肽的表达也增加。血小板反应蛋白的增加与血小板衍生生长因子（PDGF）所观察到的情况形成鲜明对比，PDGF可诱导血小板反应蛋白mRNA水平快速短暂升高。尽管TGF-β1能够直接增强血小板反应蛋白以及生长相关基因c-fos和c-myc的表达，并且诱导c-fos表达的动力学与PDGF相同，但它在三种独立的平滑肌细胞系中均无法引发[3H]胸腺嘧啶掺入DNA。然而，TGF-β1能够强烈增强SMC对PDGF的有丝分裂反应。将TGF-β1和PDGF同时添加到SMC中也会导致血小板反应蛋白以及c-myc的表达协同增加。有趣的是，在另一种平滑肌细胞系中，观察到对单独的TGF-β1有微弱且延迟的有丝分裂反应。我们的结果有力地表明，TGF-β1和PDGF诱导血小板反应蛋白表达的机制不同。此外，TGF-β1能够增强PDGF诱导的有丝分裂可能是由于TGF-β1能够直接诱导血小板反应蛋白、c-fos、c-myc和PDGFβ受体的表达。
