Department of Ophthalmology, The PLA General Hospital, Beijing, China (mainland).
Med Sci Monit. 2017 Dec 3;23:5744-5751. doi: 10.12659/msm.905336.
BACKGROUND Diabetic retinopathy (DR) is one of the most common and serious complications of diabetes mellitus (DM). The autophagy-lysosome pathway (ALP) is one of the main intracellular self-digestive degradation systems. Lysosomal impairment and autophagic dysfunction are early events in the pathogenesis of DR, suggesting autophagy might be a novel therapeutic strategy for DR treatment. MATERIAL AND METHODS In our study, we screened a differentially expressed miRNA, miR-1273g-3p, in streptozotocin (STZ)-injected DR rat retinal pigment epithelial (RPE) cells. miR-1273g-3p inhibitor and mimic were employed to treat RPE cells to assess the role of miR-1273g-3p. QRT-PCR and Western blot analysis were performed to examine the function of miR-1273g-3p on ALP-related and DR-related proteins. RESULTS miR-1273g-3p was highly expressed in STZ-induced DM RPE cells. miR-1273g-3p mimic promoted the expression of DR-related MMP-2, MMP-9, and TNF-α proteins, and ALP-related LC3, cathepsin B, and cathepsin L factors, but miR-1273g-3p inhibitor suppressed the levels of these factors. CONCLUSIONS miR-1273g-3p is involved in the progression of DR by modulating the autophagy-lysosome pathway. These findings provided new evidence of the close relationship between DR and ALP, and reveal a new target for DR therapy.
糖尿病视网膜病变（DR）是糖尿病（DM）最常见和最严重的并发症之一。自噬溶酶体途径（ALP）是主要的细胞内自我消化降解系统之一。溶酶体损伤和自噬功能障碍是 DR 发病机制中的早期事件，表明自噬可能是 DR 治疗的一种新的治疗策略。
在我们的研究中，我们筛选了链脲佐菌素（STZ）注射的 DR 大鼠视网膜色素上皮（RPE）细胞中差异表达的 miRNA，miR-1273g-3p。使用 miR-1273g-3p 抑制剂和模拟物处理 RPE 细胞，以评估 miR-1273g-3p 的作用。采用 QRT-PCR 和 Western blot 分析检测 miR-1273g-3p 对 ALP 相关和 DR 相关蛋白的作用。
miR-1273g-3p 在 STZ 诱导的 DM RPE 细胞中高表达。miR-1273g-3p 模拟物促进了 DR 相关 MMP-2、MMP-9 和 TNF-α 蛋白以及 ALP 相关 LC3、组织蛋白酶 B 和组织蛋白酶 L 因子的表达，而 miR-1273g-3p 抑制剂则抑制了这些因子的水平。
miR-1273g-3p 通过调节自噬溶酶体途径参与 DR 的进展。这些发现为 DR 与 ALP 之间的密切关系提供了新的证据，并揭示了 DR 治疗的新靶点。
