Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promoting self-renewal in retinal stem cells remain unknown. We found that melatonin can significantly increase proliferation and enhance expression of a stem cell marker, nestin, in retinal neural stem cells (NSCs) via melatonin receptor 1 (MT1). The ERK pathway inhibitor SCH772984 and TGF-β pathway inhibitor SB431542 were used to study the melatonin-mediated molecular mechanisms of cell proliferation in NSCs. The results revealed a novel molecular mechanism of melatonin promotion of self-renewal of NSCs in which a chain reaction in the ERK and TGF-β/Smad pathways promotes self-renewal and transcription of nestin. In addition, dual-luciferase assays revealed that Smad4 directly regulated nestin transcription after melatonin treatment in NSCs. These findings revealed novel mechanisms through which the ERK pathway cooperates with the Smad pathway to regulate self-renewal in NSCs to enhance nestin expression.

中文翻译：

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褪黑激素可促进视网膜神经干细胞的自我更新和巢蛋白表达。

尽管褪黑素已显示出多种生物学功能，但其对促进视网膜干细胞自我更新的作用仍然未知。我们发现褪黑激素可以通过褪黑激素受体1（MT1）显着增加视网膜神经干细胞（NSC）中的干细胞标记物Nestin的增殖并增强其表达。ERK途径抑制剂SCH772984和TGF-β途径抑制剂SB431542用于研究褪黑素介导的NSCs细胞增殖的分子机制。结果揭示了褪黑激素促进NSCs自我更新的新分子机制，其中ERK和TGF-β/ Smad途径的链反应促进巢蛋白的自我更新和转录。此外，双荧光素酶测定法显示，在神经干细胞中褪黑激素处理后，Smad4直接调节巢蛋白的转录。