Abstract：
BACKGROUND: Cataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive.
RESULTS: The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model.
CONCLUSIONS: Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC.
RESULTS: The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model.
CONCLUSIONS: Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC.
摘要：
背景：白内障在全球范围内导致视力障碍，糖尿病加速白内障的形成和进展。在这里，我们发现miR-204-5p的表达水平在白内障患者晶状体前囊的晶状体上皮中减少，在糖尿病性白内障（DC）患者中下降更明显。然而,miR-204-5p在DC发育过程中的作用和机制仍然难以捉摸。
结果：在DC患者晶状体前囊的晶状体上皮和H2O2诱导的人晶状体上皮细胞（HLEC）白内障模型中，线粒体膜电位（MMP）降低，提示线粒体功能受损。始终如一，特定抑制剂的miR-204-5p敲低也减弱了HLEC中的MMP。使用生物信息学和荧光素酶测定，进一步通过免疫荧光染色和蛋白质印迹，我们鉴定了胰岛素样生长因子结合蛋白IGFBP5，作为miR-204-5p在HLECs中的直接靶标。IGFBP5在DC患者晶状体前囊的晶状体上皮和HLEC白内障模型中表达上调，IGFBP5敲低可以逆转HLEC白内障模型的线粒体功能障碍。
结论：我们的结果表明miR-204-5p通过抑制IGFBP5维持线粒体功能的完整性，并揭示IGFBP5可能是DC新的治疗靶点和预后因子。
结果：在DC患者晶状体前囊的晶状体上皮和H2O2诱导的人晶状体上皮细胞（HLEC）白内障模型中，线粒体膜电位（MMP）降低，提示线粒体功能受损。始终如一，特定抑制剂的miR-204-5p敲低也减弱了HLEC中的MMP。使用生物信息学和荧光素酶测定，进一步通过免疫荧光染色和蛋白质印迹，我们鉴定了胰岛素样生长因子结合蛋白IGFBP5，作为miR-204-5p在HLECs中的直接靶标。IGFBP5在DC患者晶状体前囊的晶状体上皮和HLEC白内障模型中表达上调，IGFBP5敲低可以逆转HLEC白内障模型的线粒体功能障碍。
结论：我们的结果表明miR-204-5p通过抑制IGFBP5维持线粒体功能的完整性，并揭示IGFBP5可能是DC新的治疗靶点和预后因子。
