PI3K/AKT/mTOR 信号通路参与胰岛素介导的视网膜色素上皮细胞病理性近视相关因子的调节。
PI3K/AKT/mTOR signaling participates in insulin-mediated regulation of pathological myopia-related factors in retinal pigment epithelial cells.
机构信息
Ophthalmology Department, 2nd People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, No. 176 Qingnian Road, Wuhua District, Yunnan Province, 650021, Kunming, China.
Orthopedics and Traumatology Department, 2nd People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, 650021, Kunming, Yunnan Province, China.
出版信息
BMC Ophthalmol. 2021 May 17;21(1):218. doi: 10.1186/s12886-021-01946-y.
BACKGROUND
Insulin positively correlates with the length of the eye axis and is increased in the vitreous and serum of patients with pathological myopia (PM). How insulin influences the physiological process of retinal pigment epithelial (RPE) cells in PM remains unclear. This study aimed to explore the effect of insulin on the ultrastructure and function of RPE cells and the role of PI3K/AKT/mTOR signaling involved in the development of PM.
METHODS
The ARPE-19 cells were treated with different concentrations of insulin to analyze the cell morphology, cell viability, the protein level of insulin receptor β, and the mRNA and protein levels of and PM-related factors (TIMP-2, MMP-2, bFGF, and IGF-1). The ultrastructure of APRE-19 cells was also observed after insulin treatment. Besides, the PI3K/AKT/mTOR signaling was studied with or without the PI3K inhibitor LY294002 in ARPE-19 cells.
RESULTS
Insulin enhanced the cell viability of ARPE-19 cells and caused the endoplasmic reticulum to expand and vesiculate, suggesting increased secretion of growth factors and degeneration in ARPE-19 cells. Furthermore, the insulin receptor β was stimulated with insulin treatment, subsequently, the phosphorylation of AKT and mTOR was positively activated, which was adversely suppressed in the presence of LY294002. The secretion of TIMP-2 and bFGF was significantly decreased, and the secretion of MMP-2 and IGF-1 was highly elevated with insulin treatment depending on the concentration in ARPE-19 cells. Furthermore, the effect of insulin on PM-related proteins was restored with the addition of LY294002.
CONCLUSIONS
Our results indicated that insulin regulated the secretion of PM-related factors via the PI3K/AKT/mTOR signaling pathway in retinal pigment epithelial cells, and thus probably promoted the development of PM through transducing regulation signals from retina to choroid and sclera.
背景
胰岛素与眼轴长度呈正相关，在病理性近视（PM）患者的玻璃体和血清中增加。胰岛素如何影响 PM 中视网膜色素上皮（RPE）细胞的生理过程尚不清楚。本研究旨在探讨胰岛素对 RPE 细胞超微结构和功能的影响，以及涉及 PM 发生发展的 PI3K/AKT/mTOR 信号通路的作用。
方法
用不同浓度的胰岛素处理 ARPE-19 细胞，分析细胞形态、细胞活力、胰岛素受体β蛋白水平以及与 PM 相关的因子（TIMP-2、MMP-2、bFGF 和 IGF-1）的 mRNA 和蛋白水平。用胰岛素处理后还观察了 APRE-19 细胞的超微结构。此外，在 ARPE-19 细胞中用或不用 PI3K 抑制剂 LY294002 研究了 PI3K/AKT/mTOR 信号通路。
结果
胰岛素增强了 ARPE-19 细胞的细胞活力，并导致内质网扩张和形成小泡，表明生长因子的分泌增加和 ARPE-19 细胞的变性。此外，胰岛素处理刺激胰岛素受体β，随后 AKT 和 mTOR 的磷酸化被正向激活，而在 LY294002 存在下则被抑制。TIMP-2 和 bFGF 的分泌显著减少，而 MMP-2 和 IGF-1 的分泌则随着 ARPE-19 细胞中胰岛素浓度的增加而显著升高。此外，在用 LY294002 处理后，胰岛素对 PM 相关蛋白的作用得到恢复。
结论
我们的结果表明，胰岛素通过视网膜色素上皮细胞中的 PI3K/AKT/mTOR 信号通路调节 PM 相关因子的分泌，从而可能通过从视网膜向脉络膜和巩膜传递调节信号来促进 PM 的发展。
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