Oncotarget

Research Papers:

Wogonin induces retinal neuron-like differentiation of bone marrow stem cells by inhibiting Notch-1 signaling

Qinmeng Shu, Hong Zhuang, Jiawen Fan, Xin Wang and Gezhi Xu _

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Oncotarget. 2017; 8:28431-28441. https://doi.org/10.18632/oncotarget.16085

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Abstract

Qinmeng Shu1,2, Hong Zhuang1,2, Jiawen Fan1,2, Xin Wang1,2, Gezhi Xu1,2

1Department of Ophthalmology and Vision Sciences, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

2Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, People’s Republic of China

Correspondence to:

Gezhi Xu, email: gezhixu@126.com

Keywords: wogonin, bone marrow stem cells, Notch-1, retinal degenerative diseases, differentiation

Received: January 04, 2017     Accepted: February 28, 2017     Published: March 10, 2017

ABSTRACT

Age-related macular degeneration and retinitis pigmentosa are major causes of irreversible vision loss in the elderly and, despite sustained efforts, current treatments are largely ineffective. Wogonin is a bioactive plant flavonoid possessing a range of beneficial properties, including neuroprotective effects. We investigated the ability of wogonin to promote retinal neuron-like differentiation of bone marrow stem cells (BMSCs) and assessed the involvement of Notch-1 signaling in this process. Cultured mouse BMSCs were left untreated or exposed to neurotrophic factors in the presence or absence of wogonin, and western blotting, RT-PCR and immunofluorescence were used to identify changes in molecular markers of stemness and neuroretinal differentiation. Proteins in the Notch-1 signaling pathway, a main negative regulator of neurogenesis, were also examined by western blotting. We found that expression of stem cell markers was reduced, while markers of mature retinal neurons, bipolar cells and photoreceptors were increased in wogonin-treated BMSCs. Wogonin also dose-dependently decreased expression of Notch-1 signaling proteins. Moreover, blockade of Notch-1 both mimicked and enhanced the effect of wogonin to facilitate BMSC differentiation into retinal neuron-like cells. Wogonin thus appears to promote retinal neuron-like differentiation of BMSCs by antagonizing the inhibitory actions of Notch-1 signaling on neurogenesis and may be useful in the treatment of retinal degenerative diseases.


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