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胰岛素样生长因子-1 对视网膜祖细胞增殖和分化的调节作用。

Insulin-like growth factor-1 regulation of retinal progenitor cell proliferation and differentiation.

机构信息

a Department of Ophthalmology, Ninth People's Hospital , Shanghai JiaoTong University School of Medicine , Shanghai , 200011 , P.R. China.

b Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai , 200011 , P.R. China.

出版信息

Cell Cycle. 2018;17(4):515-526. doi: 10.1080/15384101.2018.1431594. Epub 2018 Apr 3.

Abstract

Strategies to improve retinal progenitor cell (RPC) capacity to yield proliferative and multipotent pools of cells that can efficiently differentiate into retinal neurons, including photoreceptors, could be vital for cell therapy in retinal degenerative diseases. In this study, we found that insulin-like growth factor-1 (IGF-1) plays a role in the regulation of proliferation and differentiation of RPCs. Our results show that IGF-1 promotes RPC proliferation via IGF-1 receptors (IGF-1Rs), stimulating increased phosphorylation in the PI3K/Akt and MAPK/Erk pathways. An inhibitor experiment revealed that IGF-1-induced RPC proliferation was inhibited when the PI3K/Akt and MAPK/Erk pathways were blocked. Furthermore, under the condition of differentiation, IGF-1-pretreated RPCs prefer to differentiate into retinal neurons, including photoreceptors, in vitro, which is crucial for visual formation and visual restoration. These results demonstrate that IGF-1 accelerates the proliferation of RPCs and IGF-1 pretreated RPCs may have shown an increased potential for retinal neuron differentiation, providing a novel strategy for regulating the proliferation and differentiation of retinal progenitors in vitro and shedding light upon the application of RPCs in retinal cell therapy.

摘要

提高视网膜祖细胞 (RPC) 产生增殖和多能细胞池的能力的策略,这些细胞可以有效地分化为视网膜神经元,包括光感受器,对于视网膜退行性疾病的细胞治疗可能至关重要。在这项研究中,我们发现胰岛素样生长因子-1 (IGF-1) 在调节 RPC 的增殖和分化中起作用。我们的结果表明,IGF-1 通过 IGF-1 受体 (IGF-1Rs) 促进 RPC 增殖,刺激 PI3K/Akt 和 MAPK/Erk 途径的磷酸化增加。抑制剂实验表明,当阻断 PI3K/Akt 和 MAPK/Erk 途径时,IGF-1 诱导的 RPC 增殖受到抑制。此外,在分化条件下,IGF-1 预处理的 RPC 更倾向于在体外分化为视网膜神经元,包括光感受器,这对于视觉形成和视觉恢复至关重要。这些结果表明,IGF-1 加速了 RPC 的增殖,IGF-1 预处理的 RPC 可能表现出增加的视网膜神经元分化潜力,为体外调节视网膜祖细胞的增殖和分化提供了一种新策略,并为 RPC 在视网膜细胞治疗中的应用提供了启示。

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