College of Basic Medicine, Jining Medical University, Jining, Shandong Province, R.P. China.
Institute of Precision Medicine, Jining Medical University, Jining, Shandong Province, R.P. China.
Histol Histopathol. 2019 Jun;34(6):645-654. doi: 10.14670/HH-18-065. Epub 2018 Nov 16.
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.
尽管褪黑素表现出多种生物学功能，但它对促进视网膜干细胞自我更新的影响尚不清楚。我们发现褪黑素通过褪黑素受体 1（MT1）可显著增加视网膜神经干细胞（NSCs）的增殖并增强干细胞标志物巢蛋白的表达。ERK 通路抑制剂 SCH772984 和 TGF-β 通路抑制剂 SB431542 用于研究褪黑素介导的 NSCs 细胞增殖的分子机制。结果揭示了褪黑素促进 NSCs 自我更新的新分子机制，即 ERK 和 TGF-β/Smad 通路的连锁反应促进巢蛋白的自我更新和转录。此外，双荧光素酶报告基因实验显示，褪黑素处理后 Smad4 可直接调控 NSCs 中巢蛋白的转录。这些发现揭示了 ERK 通路与 Smad 通路合作调节 NSCs 自我更新以增强巢蛋白表达的新机制。
