Cell migration-promoting and apoptosis-inhibiting activities of Bm-TFF2 require distinct structure basis.
Cell migration-promoting and apoptosis-inhibiting activities of Bm-TFF2 require distinct structure basis.
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DOI：
10.1016/j.bbrc.2010.08.137
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发表时间：
2010-10
影响因子：
3.1
通讯作者：
Guoyu Yu;Yong Zhang;Y. Xiang;P. Jiang;Zhongming Chen;Wenhui Lee;Yun Zhang
中科院分区：
文献类型：
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作者：
Guoyu Yu;Yong Zhang;Y. Xiang;P. Jiang;Zhongming Chen;Wenhui Lee;Yun Zhang
人三叶因子（Human trefoil factors, TFFs）通过刺激细胞迁移和抑制细胞凋亡，在胃肠道创面愈合、上皮修复和抗炎等方面发挥重要作用。在我们之前的研究中，从青蛙bomina maxima皮肤分泌物中分离到的两栖动物三叶因子Bm-TFF2的活性比人类三叶因子强得多。我们认为重组Bm-TFF2的体外表达有助于破译其在两栖动物皮肤修复中的作用。Bm-TFF2含有12个半胱氨酸残基，并具有两个tff结构域。在这项研究中，我们表达了Bm-TFF2的全长及其单域截断（Bm-TFF2- d1和Bm-TFF2- d2，每个都包含一个Bm-TFF2的单域）。重组蛋白，包括Bm-TFF2的全长及其单域截断，可以促进人上皮AGS细胞的迁移和大鼠肠上皮IEC-6细胞的伤口愈合。然而，只有全长的Bm-TFF2能抑制神经酰胺诱导的AGS细胞凋亡，而其单域截断不能。综上所述，这是首次使用重组Bm-TFF2及其截断片段来研究其结构-功能关系。并且我们报道了Bm-TFF2的全长和每个结构域都能诱导细胞迁移，但只有Bm-TFF2的全长才能抑制细胞凋亡，这表明Bm-TFF2促进细胞迁移和抑制细胞凋亡的活性需要不同的结构基础。
Human trefoil factors (TFFs) play an important role in wound healing, epithelial restitution and anti-inflammatory effects in the gastrointestinal tract by stimulating cell migration and inhibiting cell apoptosis. In our previous study, Bm-TFF2, an amphibian trefoil factor, which is isolated from the skin secretions of frog Bombina maxima, has much stronger activities than human TFFs. We believe that the expression of the recombinant Bm-TFF2 in vitro is useful to decipher its role in amphibian skin repair. Bm-TFF2 contains 12 cysteine residues and has two TFF-domains. In this study, we expressed full-length of Bm-TFF2 and its single-domain truncations (Bm-TFF2-D1 and Bm-TFF2-D2, each contains a single TFF-domain of Bm-TFF2). The recombinant proteins, including full-length and its single-domain truncations of Bm-TFF2, can promote the migration of human epithelial AGS cells and wound healing of rat intestinal epithelial IEC-6 cells. However, only the full-length of Bm-TFF2, but not its single-domain truncations, can inhibit ceramide-induced apoptosis in AGS cells. In summary, it is the first time to use the recombinant Bm-TFF2 and its truncations to investigate its structure–function relationship. And we report that full-length and each domain of Bm-TFF2 can induce cell migration but only the full-length of Bm-TFF2 can suppress apoptosis, indicating that cell migration-promoting and apoptosis-inhibiting activities of Bm-TFF2 require distinct structure basis.