Differential proliferative response of fetal and adult human skin fibroblasts to transforming growth factor-β
Differential proliferative response of fetal and adult human skin fibroblasts to transforming growth factor-β
复制标题
DOI：
10.1111/j.1067-1927.2004.12305.x
复制
发表时间：
2004-05-01
影响因子：
2.9
通讯作者：
Kletsas, D
中科院分区：
文献类型：
--
作者：
Pratsinis, H;Giannouli, CC;Kletsas, D
由于胎儿和成人修复过程之间存在明显差异，我们研究了这两个阶段皮肤成纤维细胞对转化生长因子- β (tgf - β)的增殖反应，tgf - β是一种在组织修复中具有广泛活性的细胞因子。在这里，我们提出了tgf - β抑制胎儿人类皮肤成纤维细胞的证据，而它对成人皮肤成纤维细胞有刺激作用。tgf - β的这种增殖作用是浓度依赖性的，但与异构体依赖性。此外，即使细胞短暂暴露于这种生长因子，也足以发挥其刺激或抑制作用。因此，我们研究了tgf - β在主要信号通路中引起的即时反应，我们发现它诱导SMAD通路的快速激活，即SMAD2的磷酸化和核易位，随后去磷酸化，很可能是由于蛋白酶体的降解。然而，在胎儿和成人成纤维细胞中观察到类似的激活强度和动力学。另一方面，姜黄素是一种具有伤口愈合特性的天然产物，可抑制几种细胞内信号通路，研究发现姜黄素完全消除了tgf - β 1对人胎儿皮肤成纤维细胞的抑制作用，而不影响对成年供体成纤维细胞的刺激作用。总之，胎儿和成人皮肤成纤维细胞对tgf - β的增殖反应中存在一个主要的自由基，可能反映了这两个发育阶段所遵循的不同修复策略。
Since pronounced differences exist between the fetal and adult repair processes, we studied the proliferative response of skin fibroblasts from these two stages to transforming growth factor-beta (TGF-beta), a cytokine with a broad range of activities in tissue repair. Here, we present evidence that TGF-beta inhibits fetal human skin fibroblasts, while it is stimulatory for adult ones. This proliferative effect of TGF-beta was found to be concentration-dependent, but isoform-in dependent. Furthermore, even a transient exposure of the cells to this growth factor was sufficient to exert its stimulatory or inhibitory action. Accordingly, we have studied the immediate responses provoked by TGF-beta in major signaling pathways, and we have found that it induces a rapid activation of the SMAD pathway, i.e., phosphorylation and nuclear translocation of SMAD2, followed by dephosphorylation, most probably due to degradation by the proteasome, However, similar intensity and kinetics of this activation have been observed in both fetal and adult fibroblasts. On the other hand, curcumin, a natural product with wound healing properties that inhibits several intracellular signaling pathways, was found to completely abrogate the inhibitory effect of TGF-beta1 on human fetal skin fibroblasts, without affecting the stimulatory action on fibroblasts from adult donors. In conclusion, there is a major radical in the proliferative response of fetal and adult human skin fibroblasts to TGF-beta, possibly reflecting the different repair strategies followed in these two stages of development.