Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Sanxiang Road 1055, Suzhou, 215004, Jiangsu, China.
Int Ophthalmol. 2022 Feb;42(2):661-676. doi: 10.1007/s10792-021-02038-y. Epub 2021 Nov 18.
Diabetic retinopathy (DR) is one of the leading causes of blindness in working-aged people. Few studies were on the relationship between S100 Calcium Binding Protein A9 (S100A9) protein and DR, and none on endothelial cells induced by tasquinimod in high glucose. Therefore, we assessed the relationship between tasquinimod and S100A9 in DR.
DR pathogenesis was simulated using high-glucose-induced human retinal endothelial cells (HRECs) to study the mRNA expression of s100a9, thrombospondin-1 (tsp-1), hypoxia-inducible factor 1-alpha (hif1-α), intercellular adhesion molecule 1 (icam-1), and vascular endothelial growth factor (vegf) after tasquinimod treatment. The protein expression of S100A9, TSP-1, extracellular signal-regulated kinase (ERK), ICAM-1 and VEGF was also analyzed.
A total of 28 eyes of 26 patients were included in this experiment. A significantly higher expression of S100A9 as well as enhanced proliferation and mobility was observed in the high-glucose-treated HRECs compared with that in low-glucose-treated cells. However, these were significantly inhibited when treated with high glucose with 50 μM tasquinimod. The mRNA expression of tsp-1 was increased, whereas that of hif1-α, icam-1 and vegf was decreased after tasquinimod treatment. Western blot indicated the increased TSP-1 but decreased ERK, ICAM-1 and VEGF expression after treating with tasquinimod.
High glucose promoted the expression of s100a9, S100A9 protein in DR patients and HRECs. Tasquinimod inhibited the proliferation, migration and lumen formation of HRECs under a high glucose environment. Tasquinimod might play a vital role in inhibiting angiogenesis through inducing TSP-1 and inhibiting VEGF, ICAM-1 and ERK.
糖尿病视网膜病变（DR）是导致工作年龄段人群失明的主要原因之一。很少有研究关注 S100 钙结合蛋白 A9（S100A9）蛋白与 DR 的关系，也没有研究涉及高糖环境下tasquinimod 对内皮细胞的影响。因此，我们评估了 tasquinimod 与 DR 中 S100A9 的关系。
采用高糖诱导人视网膜内皮细胞（HRECs）模拟 DR 发病机制，研究 tasquinimod 处理后 s100a9、血小板反应蛋白-1（TSP-1）、缺氧诱导因子 1-α（HIF1-α）、细胞间黏附分子 1（ICAM-1）和血管内皮生长因子（VEGF）的 mRNA 表达。还分析了 S100A9、TSP-1、细胞外信号调节激酶（ERK）、ICAM-1 和 VEGF 的蛋白表达。
本实验共纳入 26 例 28 只眼。与低糖处理的细胞相比，高糖处理的 HRECs 中 S100A9 的表达明显升高，增殖和迁移能力增强。然而，当用 50 μM tasquinimod 处理高糖时，这些现象明显受到抑制。TSP-1 的 mRNA 表达增加，而 HIF1-α、ICAM-1 和 VEGF 的表达减少。Western blot 表明，tasquinimod 处理后 TSP-1 表达增加，ERK、ICAM-1 和 VEGF 表达减少。
高糖促进了 DR 患者和 HRECs 中 S100A9 的表达。tasquinimod 抑制了高糖环境下 HRECs 的增殖、迁移和管腔形成。tasquinimod 通过诱导 TSP-1 和抑制 VEGF、ICAM-1 和 ERK 可能在抑制血管生成中发挥重要作用。
