Thannickal V J, Aldweib K D, Rajan T, Fanburg B L
Department of Medicine, New England Medical Center/Tupper Research Institute/Tufts University, School of Medicine, Boston, Massachusetts, 02111, USA.
Biochem Biophys Res Commun. 1998 Oct 20;251(2):437-41. doi: 10.1006/bbrc.1998.9443.
Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that induces mesenchymal cell proliferation in vivo while inhibiting growth of most cells directly via serine-threonine receptor(s) binding/activation in vitro. In this study, the ability of TGF-beta1 to regulate the receptor expression of classical mitogenic growth factors that bind receptor tyrosine kinases was examined. TGF-beta1 markedly increased the protein expression of the fibroblast growth factor (FGF) receptors FGFR-1 (Flg) and FGFR-2 (Bek) in a time- and dose-dependent manner in human lung fibroblasts. This resulted in a potentiation of the mitogenic response of multiple FGF ligands that bind to these receptors. TGF-beta1 had no effect on epidermal growth factor (EGF) or platelet-derived growth factor (PDGF)-beta receptor expression and the mitogenic responses mediated by specific ligands for these receptors were not increased. These results demonstrate a novel action of TGF-beta1 to selectively upregulate the expression of FGF receptor family members leading to enhanced mitogenesis by FGFs.
转化生长因子-β1（TGF-β1）是一种多功能细胞因子，它在体内诱导间充质细胞增殖，而在体外通过与丝氨酸-苏氨酸受体结合/激活直接抑制大多数细胞的生长。在本研究中，检测了TGF-β1调节与受体酪氨酸激酶结合的经典促有丝分裂生长因子受体表达的能力。TGF-β1在人肺成纤维细胞中以时间和剂量依赖性方式显著增加成纤维细胞生长因子（FGF）受体FGFR-1（Flg）和FGFR-2（Bek）的蛋白表达。这导致与这些受体结合的多种FGF配体的促有丝分裂反应增强。TGF-β1对表皮生长因子（EGF）或血小板衍生生长因子（PDGF）-β受体表达没有影响，并且由这些受体的特异性配体介导的促有丝分裂反应也没有增加。这些结果证明了TGF-β1的一种新作用，即选择性上调FGF受体家族成员的表达，导致FGFs增强有丝分裂。
