Melatonin promotes self-renewal and nestin expression in neural stem cells from the retina
Yuhua Gao1,2,3, Li Ma4, Chunyu Bai1,2,3, Xiangyang Zhang1,2 and Wancai Yang1,2
1College of Basic Medicine, 2Institute of Precision Medicine, Jining Medical University, Jining, Shandong Province, 3Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing and 4Jining First People's Hospital and the Affiliated Hospital of Jining Medical University, Jining, R.P. China
Gao Yuhua and Ma Li contributed equally to this study
Offprint requests to: Yuhua Gao and Chunyu Bai, 133 Hehua Road, Jining, Shandong Province, 272067, R.P. China. e-mail: chunyu_bai@hotmail.com and anngyh@126.com
Summary. 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. Histol Histopathol 34, 645-654 (2019)
Key words: Retina, Neural stem cells, Melatonin, Cell proliferation, Nestin expression
DOI: 10.14670/HH-18-065