IGFBP-3 mediates TGF-β1-induced cell growth in human airway smooth muscle cells
IGFBP-3 mediates TGF-β1-induced cell growth in human airway smooth muscle cells
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DOI：
10.1152/ajplung.2000.278.3.l545
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发表时间：
2000-03-01
影响因子：
4.9
通讯作者：
Herrick, DJ
中科院分区：
文献类型：
--
作者：
Cohen, P;Rajah, R;Herrick, DJ
2000.-胰岛素样生长因子结合蛋白-3（IGFBP-3）和转化生长因子-β（TGF-β）已分别显示具有细胞特异性生长抑制或生长增强作用。TGF-β刺激多种细胞类型中IGFBP-9 mRNA和肽的表达，并且已证明TGF-β诱导的生长抑制和细胞凋亡是通过诱导IGFBP-3介导的。然而，尚未显示TGF-β和IGFBP-3诱导的生长刺激作用之间的联系。在这项研究中，我们研究了IGFBP-3在介导TGF-β 1诱导的细胞生长中的作用，使用人气道平滑肌（ASM）细胞作为我们的模型。TGF-β 1（1 ng/ml）处理诱导IGFBP-3 mRNA和蛋白表达水平增加10- 20倍。向生长培养基中添加IGFBP-3或TGF-β 1导致细胞增殖增加约两倍。将ASM细胞与IGFBP-3反义寡聚体（而非正义寡聚体）以及IGFBP-3中和抗体（而非对照IgG）共孵育可阻断TGF-β 1诱导的生长（P < 0.001）。在ASM细胞裂解物中观察到几种IGFBP-3相关蛋白，其可能在对IGFBP-3的细胞应答中起作用。这些发现表明IGFBP-3能够介导TCF-β在ASM细胞中的生长刺激作用。
2000.-Both insulin-like growth factor binding protein-3 (IGFBP-3) and transforming growth factor-beta (TGF-beta) have been separately shown to have cell-specific growth-inhibiting or growth-potentiating effects. TGF-beta stimulates IGFBP-9 mRNA and peptide expression in several cell types, and TGF-beta-induced growth inhibition and apoptosis have been shown to be mediated through the induction of IGFBP-3. However,a link between the growth stimulatory effects of TGF-beta and IGFBP-3-induction has not been shown. In this study, we investigated the role of IGFBP-3 in mediating TGF-beta 1-induced cell growth using human airway smooth muscle (ASM) cells as our model. TGF-beta 1 (1 ng/ml) treatment induced a 10- to 20-fold increase in the levels of expression of IGFBP-3 mRNA and protein. Addition of either IGFBP-3 or TGF-beta 1 to the growth medium resulted in an approximately twofold increase in cell proliferation. Coincubation of ASM cells with IGFBP-3 antisense (but not sense) oligomers as well as with an IGFBP-3 neutralizing antibody (but not with control IgG) blocked the growth induced by TGF-beta 1 (P < 0.001). Several IGFBP-3-associated proteins were observed in ASM cell lysates, which may have a role in the cellular responses to IGFBP-3. These findings demonstrate that IGFBP-3 is capable of mediating the growth stimulatory effect of TCF-beta in ASM cells.