PDF(Pubmed)
Abstract：
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.
摘要：
血管内皮细胞的损伤是糖尿病视网膜病变(DR)发生发展的关键因素。已经报道了PDLIM1(PDZ和LIM蛋白家族的成员)在血管疾病中发挥重要功能。本研究旨在阐明PDLIM1对DR中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途径中起关键作用。然而,在DR中没有发现深入的报告。用高糖高脂(HG/HL)培养基处理视网膜毛细血管内皮细胞(RCEC),和siRNA转染来研究PDLIM1在DR中的作用。通过qRT-PCR和蛋白质印迹确认PDLIM1和Wnt3a表达。流式细胞术,Transwell分析，和划痕试验用于测试细胞凋亡的能力，迁移,和入侵。PDLIM1主要表达于视网膜色素上皮(RPE),神经节细胞层（GCL），内丛层（IPL），和外丛层（OPL）。HG/HL增加Wnt3a水平，促进细胞凋亡能力，迁移,和入侵,通过PDLIM1的敲低而逆转。发现PDLIM1通过反调节Wnt3a在糖尿病视网膜病变中起保护作用。PDLIM1改善细胞凋亡，迁移,通过负调控DR的RCEC中的Wnt3a和入侵，这表明PDLIM1可能是DR治疗的一个有希望的治疗靶点。
