Vascular cells respond differentially to transforming growth factors beta 1 and beta 2 in vitro.
Vascular cells respond differentially to transforming growth factors beta 1 and beta 2 in vitro.
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发表时间：
1991
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通讯作者：
Rae Merwin;W. Newman;L. Dawson;BeaIl;A. Tucker;J. Madri
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作者：
Rae Merwin;W. Newman;L. Dawson;BeaIl;A. Tucker;J. Madri
转化生长因子β 1（TGF-β 1）和β 2（TGF-β 2）在许多细胞系统研究中是等效的。然而，最近的数据显示，这两种生长因子在特定的生物系统中引起不同的影响。本研究比较了TGF-β 1和TGF-β 2牛主动脉内皮细胞（BAECs）、大鼠附睾脂肪垫微血管内皮细胞（RFCs）和牛主动脉平滑肌细胞（BASCs）的作用。在二维培养中，BAECs、BASMCs和RFC的增殖都受到TGF-β 1的抑制，而在对TGF-β 2的反应中，BASMCs完全受到抑制，RFC受到适度抑制，BAECs不受影响。牛主动脉内皮细胞迁移显著抑制TGF-β 1，但只有轻微抑制TGF-β 2。与此相反，BASMC迁移增强TGF-β 1，并不受TGF-β 2。在三维培养物中，RFCs被刺激进行体外血管生成，以响应10倍高浓度的TGF-β 1和TGF-β 2。三种不同的受体检测证明了BAEC、BASMCs和RFC上存在I型和II型TGF-β 1细胞表面结合蛋白。标记的TGF-β 1与100倍摩尔过量的未标记的TGF-β 1完全竞争，但仅与等量过量的未标记的TGF-β 2部分竞争。此外，这三种血管细胞类型中I型与II型TGF-β受体的比例从BAEC中的1：1到RFC中的1.5：1到BASMC中的3：1不等，并且可以与在增殖、迁移和体外血管生成测定中对TGF-β 1和TGF-β 2的细胞应答的差异相关。这些发现支持了对TGF-β有不同反应的假设，这取决于细胞类型和实验条件以及所用的TGF-β浓度和同种型。
Transforming growth factor beta 1 (TGF-beta 1) and beta 2 (TGF-beta 2) are equipotent in many cell systems studies thus far. Recent data, however, show different effects elicited by these two growth factors in specific biologic systems. This investigation compares the effects of TGF-beta 1 and TGF-beta 2 bovine aortic endothelial cells (BAECs), rat epididymal fat pad microvascular endothelium (RFCs), and bovine aortic smooth muscle cells (BASCs). In two-dimensional cultures, proliferation of BAECs, BASMCs, and RFCs were all inhibited by TGF-beta 1, while in response to TGF-beta 2, BASMCs were fully inhibited, RFCs were modestly inhibited, and BAECs were unaffected. Bovine aortic endothelial cell migration was significantly inhibited by TGF-beta 1, but only slightly inhibited by TGF-beta 2. In contrast, BASMC migration was enhanced by TGF-beta 1 and was not affected by TGF-beta 2. In three-dimensional cultures, RFCs were stimulated to undergo in vitro angiogenesis in response to TGF-beta 1 and TGF-beta 2 at 10-fold higher concentrations. Three distinct receptor assays demonstrated the presence of type I and type II TGF-beta 1 cell-surface-binding proteins on BAECs, BASMCs, and RFCs. Labeled TGF-beta 1 was competed off completely with 100-fold molar excess unlabeled TGF-beta 1, but only partially with equivalent excess unlabeled TGF-beta 2. Furthermore the ratios of type I to type II TGF-beta receptors in these three vascular cell types vary from 1:1 in BAECs to 1.5:1 in RFCs to 3:1 in BASMCs and can be correlated with the differences noted in cellular responses to TGF-beta 1 and TGF-beta 2 in proliferation, migration, and in vitro angiogenic assays. These findings support the hypothesis that there are different responses to the TGF-beta s, depending on the cell type and experimental conditions as well as the TGF-beta concentration and isoform used.