Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China.
Department of Ophthalmology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
Sci Rep. 2023 Apr 10;13(1):5820. doi: 10.1038/s41598-023-33073-7.
The injury of vascular endothelial cells is a crucial factor in the development of diabetic retinopathy (DR). PDLIM1 (a member of the PDZ and LIM protein family) has been reported to exert an essential function in vascular diseases. This study aimed to elucidate the role of PDLIM1 on retinal vascular endothelial cells in DR. Immunofluorescence staining was used to localize the expression of PDLIM1 in the mouse retina. In some tumor diseases, PDLIM1 has been reported to play a key role in regulating the Wnt pathway. However, no in-depth reports have been found in DR. Retinal capillary endothelial cells (RCECs) were treated with high-glucose and high-lipid (HG/HL) culture medium, and siRNA transfection to investigate the role of PDLIM1 in DR. PDLIM1 and Wnt3a expression was confirmed by qRT-PCR and western blotting. Flow cytometry, Transwell assay, and scratch assay were used to test the ability of cell apoptosis, migration, and invasion. PDLIM1 was mainly expressed in the retinal pigment epithelium (RPE), ganglion cell layer (GCL), inner plexus layer (IPL), and outer plexus layer (OPL). HG/HL increased Wnt3a levels and promoted cell's ability of apoptosis, migration, and invasion, which were reversed by the knockdown of PDLIM1. PDLIM1 was found to play a protective role in diabetic retinopathy by counter-regulating Wnt3a. PDLIM1 ameliorates cell apoptosis, migration, and invasion by negatively regulating Wnt3a in RCECs of DR, which suggests that PDLIM1 might be a promising therapeutic target for DR treatment.
血管内皮细胞损伤是糖尿病视网膜病变（DR）发生发展的关键因素。PDLIM1（PDZ 和 LIM 蛋白家族的一员）在血管疾病中发挥着重要作用。本研究旨在阐明 PDLIM1 在 DR 中对视网膜血管内皮细胞的作用。免疫荧光染色用于定位 PDLIM1 在小鼠视网膜中的表达。在一些肿瘤疾病中，已经报道 PDLIM1 在调节 Wnt 通路中发挥关键作用。然而，在 DR 中没有发现深入的报道。用高糖和高脂（HG/HL）培养基处理视网膜毛细血管内皮细胞（RCEC），并进行 siRNA 转染以研究 PDLIM1 在 DR 中的作用。通过 qRT-PCR 和 Western blot 验证 PDLIM1 和 Wnt3a 的表达。流式细胞术、Transwell 测定和划痕试验用于测试细胞凋亡、迁移和侵袭的能力。PDLIM1 主要表达于视网膜色素上皮（RPE）、节细胞层（GCL）、内丛状层（IPL）和外丛状层（OPL）。HG/HL 增加了 Wnt3a 水平，并促进了细胞的凋亡、迁移和侵袭能力，而 PDLIM1 的敲低则逆转了这一作用。PDLIM1 通过负向调节 Wnt3a 在 DR 的 RCEC 中发挥保护作用，改善细胞凋亡、迁移和侵袭。这表明 PDLIM1 可能是治疗 DR 的有前途的治疗靶点。
