Department of Ophthalmology, The First People's Hospital of Jingmen, Jingmen, China.
Department of Ophthalmology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, China.
Bioengineered. 2022 May;13(5):13882-13892. doi: 10.1080/21655979.2022.2086351.
Diabetic retinopathy (DR) is a common complication of diabetes, and the leading cause of blindness in adults. Sprouty-related proteins with EVH1 domain (SPRED2) play an important role in diabetes and are closely related to the lens and eye morphogenesis. This study attempted to investigate the role and related mechanism of SPRED2 in DR. DR rat model was established by administration streptozocin. Human retinal endothelial cells (HRECs) were treated with high glucose (HG) to mimic DR. The results showed that SPRED2 expression was decreased in the retinal tissues of DR rats and HG-treated HRECs. MTT assay and flow cytometry data showed that SPRED2 overexpression reduced cell viability of HG-treated HRECs. SPRED2 overexpression enhanced Caspase-3 activity and promoted apoptosis of HG-treated HRECs. Furthermore, the expressions of endothelial cell markers CD31 and E-cad were down-regulated, whereas the expressions of mesenchymal cell markers FSP1, SM22, and α-SMA were up-regulated in the HG-treated HRECs. SPRED2 overexpression reversed HG-induced endothelial-mesenchymal transition in HRECs. The expressions of tight junction components claudin 3, occludin, and ZO-1 were increased in HG-treated HRECs following SPRED2 up-regulation. In addition, SPRED2 overexpression downregulated the expression of p-ERK1/2, p-p38, and p-JNK in the HG-treated HRECs. In conclusion, this study demonstrated that SPRED2 overexpression repressed endothelial-mesenchymal transition and endothelial injury in HG-treated HRECs by suppressing MAPK signaling pathway. These findings suggested that SPRED2 may be a novel potential therapeutic target implicated in DR progression.
糖尿病性视网膜病变（DR）是糖尿病的常见并发症，也是成年人失明的主要原因。具有 EVH1 结构域的 Sprouty 相关蛋白（SPRED2）在糖尿病中发挥重要作用，并且与晶状体和眼睛形态发生密切相关。本研究试图探讨 SPRED2 在 DR 中的作用及相关机制。通过给予链脲佐菌素建立 DR 大鼠模型。用高葡萄糖（HG）处理人视网膜内皮细胞（HRECs）模拟 DR。结果表明，DR 大鼠视网膜组织和 HG 处理的 HRECs 中 SPRED2 表达降低。MTT 检测和流式细胞术数据表明，SPRED2 过表达降低了 HG 处理的 HRECs 的细胞活力。SPRED2 过表达增强了 Caspase-3 活性，促进了 HG 处理的 HRECs 的凋亡。此外，HG 处理的 HRECs 中内皮细胞标志物 CD31 和 E-cad 的表达下调，而间充质细胞标志物 FSP1、SM22 和 α-SMA 的表达上调。SPRED2 过表达逆转了 HG 诱导的 HRECs 内皮-间充质转化。上调 SPRED2 后，HG 处理的 HRECs 中紧密连接成分 Claudin 3、occludin 和 ZO-1 的表达增加。此外，SPRED2 过表达下调了 HG 处理的 HRECs 中 MAPK 信号通路相关蛋白 p-ERK1/2、p-p38 和 p-JNK 的表达。综上所述，本研究表明，SPRED2 过表达通过抑制 MAPK 信号通路抑制 HG 处理的 HRECs 中内皮-间充质转化和内皮损伤。这些发现表明 SPRED2 可能是 DR 进展中一种新的潜在治疗靶点。
