Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta
Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta
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DOI：
10.1016/j.yexcr.2003.09.022
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发表时间：
2004-02-01
影响因子：
3.7
通讯作者：
Kurpakus-Wheater, M
中科院分区：
文献类型：
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作者：
Sosne, G;Xu, LH;Kurpakus-Wheater, M
胸腺素β 4（Tbeta（4））刺激上皮细胞迁移并促进层粘连蛋白-5（LM-5）表达。使用Tbeta处理的人角膜上皮细胞的基因表达分析（4），我们发现LM-5 γ 2链和转化生长因子β 1（TGF β-1）均比未处理的细胞增加2倍以上。这些发现通过RT-PCR和蛋白质水平得到证实。尽管TGF β 1以剂量依赖性方式增加LM-5的合成，但基于三个独立的实验，这似乎不是Tbeta（4）作用于LM-5 γ 2链合成的机制。在时间进程分析中，Tbeta（4）在2 h增加LM-5 γ 2链表达，并在6 h达到峰值，而TGF β-1仅在4 h增加LM-5 γ 2链表达，并在8 h达到峰值。当Tbeta 4诱导的LM-5 γ 2链表达被TGF β 1的中和抗体阻断时，LM-5 γ 2链表达增加。最后，在TGF β-1基因敲除小鼠中，Tbeta（4）使LM-5 γ 2链的表达水平高于用Tbeta（4）治疗的野生型小鼠。这些发现表明，Tbeta（4）诱导角膜上皮细胞中TGF β 1和LM-5 γ 2链的表达。TGF β 4和TGF β 1通过独立的途径增加LM-5 2 γ 2链的表达。TGF β-1的抑制进一步增加LM-5 γ 2链表达。(C)2003年爱思唯尔公司All rights reserved.
Thymosin beta 4 (Tbeta(4)) stimulates epithelial cell migration and promotes laminin-5 (LM-5) expression. Using gene expression analysis with human corneal epithelial cells treated with Tbeta(4), we find that both LM-5 gamma2 chain and transforming growth factor beta 1 (TGFbeta-1) are increased by more than 2-fold over untreated cells. These findings were confirmed by RT-PCR and at the protein level. Although TGFbeta-1 increases LM-5 synthesis in a dose-dependent manner, it does not appear to be the mechanism by which Tbeta(4) acts on LM-5 gamma2 chain synthesis based on three independent experiments. In a time-course analysis, Tbeta(4) increases LM-5 gamma2 chain expression at 2 h and peaks at 6 h, while TGFbeta-1 increases LM-5 gamma2 chain expression only at 4 h and peaks at 8 h. When Tbeta(4)-induced LM-5 gamma2 chain expression is blocked with neutralizing antibodies to TGFbeta-1, LM-5 gamma2 chain expression is increased. Finally, in TGFbeta-1 knock-out mice, Tbeta(4) increases LM-5 gamma2 chain expression to levels higher than that observed in wild-type mice treated with Tbeta(4). These findings demonstrate that Tbeta(4) induces both TGFbeta-1 and LM-5 gamma2 chain expression in corneal epithelial cells. Tbeta(4) and TGFbeta-1 increase LM-5 2 gamma2 chain expression by independent pathways. Suppression of TGFbeta-1 further increases LM-5 gamma2 chain expression. (C) 2003 Elsevier Inc. All rights reserved.