TGF-β1 signaling is essential for tissue regeneration in the Xenopus tadpole tail.

TGF-β1 signaling is essential for tissue regeneration in the Xenopus tadpole tail.
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DOI:
10.1016/j.bbrc.2021.05.082
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发表时间:
2021-08-06
影响因子:
3.1
通讯作者:
Suzuki A
Suzuki A
中科院分区:
生物学4区
文献类型:
--
作者:
Nakamura M;Yoshida H;Moriyama Y;Kawakita I;Wlizla M;Takebayashi-Suzuki K;Horb ME;Suzuki A

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两栖动物如热带爪蟾在创伤后表现出显著的组织再生能力。虽然已知转化生长因子-β(TGF-β)受体信号传导对于鱼类和两栖动物的组织再生是必不可少的,但TGF-β配体在该过程中的作用还不清楚。在这里,我们表明,抑制TGF-β1功能,防止尾巴再生爪蟾tropicalis蝌蚪。我们发现tgfb 1的表达在断尾前就存在,并在整个再生过程中持续存在。CRISPR介导的tgfb 1敲除(KO)延迟了尾部再生; tgfb 1 KO蝌蚪的表型可以通过注射tgfb 1 mRNA来拯救。细胞增殖是组织再生成功的关键事件,在tgfb 1 KO蝌蚪中下调。此外,tgfb 1 KO降低磷酸化Smad 2/3(pSmad 2/3)的表达,这对于TGF-β信号介导的细胞增殖是重要的。总的来说,我们的研究结果表明,TGF-β1通过激活Smad 2/3调节细胞增殖。因此,我们认为TGF-β1在非洲爪蟾依赖TGF-β受体的蝌蚪尾部再生中起着关键作用。
Amphibians such as Xenopus tropicalis exhibit a remarkable capacity for tissue regeneration after traumatic injury. Although transforming growth factor-β (TGF-β) receptor signaling is known to be essential for tissue regeneration in fish and amphibians, the role of TGF-β ligands in this process is not well understood. Here, we show that inhibition of TGF-β1 function prevents tail regeneration in Xenopus tropicalis tadpoles. We found that expression of tgfb1 is present before tail amputation and is sustained throughout the regeneration process. CRISPR-mediated knock-out (KO) of tgfb1 retards tail regeneration; the phenotype of tgfb1 KO tadpoles can be rescued by injection of tgfb1 mRNA. Cell proliferation, a critical event for the success of tissue regeneration, is downregulated in tgfb1 KO tadpoles. In addition, tgfb1 KO reduces the expression of phosphorylated Smad2/3 (pSmad2/3) which is important for TGF-β signal-mediated cell proliferation. Collectively, our results show that TGF-β1 regulates cell proliferation through the activation of Smad2/3. We therefore propose that TGF-β1 plays a critical role in TGF-β receptor-dependent tadpole tail regeneration in Xenopus.
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