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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >BMP signaling mediates stem/progenitor cell-induced retina regeneration
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BMP signaling mediates stem/progenitor cell-induced retina regeneration

机译：BMP信号介导干细胞/祖细胞诱导的视网膜再生

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摘要

We identified a mechanism whereby retina regeneration in the embryonic chick can be induced by the contribution of stem/ progenitor cells. We show that bone morphogenetic protein (BMP) signaling is sufficient and necessary to induce retina regeneration and that its action can be divided into two phases. By 3 days after postretinectomy (d PR), the BMP pathway directs proliferation and regeneration through the activation of Smad (canonical BMP pathway) and the up-regulation of FGF signaling by the MAPK pathway. By 7d PR, it induces apoptosis by activating p38 (a nonca-nonical BMP pathway) and down-regulating FGF signaling (by both MAPK and AKT pathways). Apoptosis at this later stage can be prevented, and BMP-induced regeneration can be further induced by inhibition of p38. These results unravel a mechanism for stem/ progenitor cell-mediated retina regeneration, where BMP activation establishes a cross-talk with the FGF pathway and selectively activates the canonical and noncanonical BMP pathways. Retina stem/progenitor cells exist in other species, including humans. Thus, our findings provide insights on how retinal stem cells can be activated for possible regenerative therapies.
机译：我们确定了一种机制，通过该机制，胚胎小鸡中的视网膜再生可以通过干/祖细胞的贡献来诱导。我们表明，骨形态发生蛋白（BMP）信号足以诱导视网膜再生，并且其作用可以分为两个阶段。视网膜切除后（d PR）3天后，BMP途径通过Smad激活（规范性BMP途径）和MAPK途径上调FGF信号传导来指导增殖和再生。通过7d PR，它可以通过激活p38（非常规BMP途径）和下调FGF信号传导（通过MAPK和AKT途径）诱导凋亡。可以预防此后阶段的凋亡，并且可以通过抑制p38进一步诱导BMP诱导的再生。这些结果揭示了干/祖细胞介导的视网膜再生的机制，其中BMP激活与FGF通路建立了串扰，并选择性地激活了规范性和非规范性BMP通路。视网膜干/祖细胞存在于其他物种中，包括人类。因此，我们的发现提供了关于如何激活视网膜干细胞进行可能的再生疗法的见解。

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