CircZNF532 敲低通过调控 miR-20b-5p/STAT3 轴保护视网膜色素上皮细胞免受高糖诱导的细胞凋亡和细胞焦亡。

CircZNF532 knockdown protects retinal pigment epithelial cells against high glucose-induced apoptosis and pyroptosis by regulating the miR-20b-5p/STAT3 axis.

机构信息

Department of Ophthalmology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

出版信息

J Diabetes Investig. 2022 May;13(5):781-795. doi: 10.1111/jdi.13722. Epub 2022 Feb 11.

INTRODUCTION

The loss of retinal pigment epithelial (RPE) cells is associated with the etiology of diabetic retinopathy (DR). This study investigated the effects of circular RNA ZNF532 (circZNF532) on apoptosis and pyroptosis of RPE cells.

MATERIALS AND METHODS

Blood samples were collected from patients with DR and healthy volunteers. A human RPE cell line ARPE-19 was induced by high glucose (HG) and assayed for cell viability, apoptosis, and pyroptosis. The binding of miR-20b-5p with circZNF532 and STAT3 was confirmed by a luciferase activity assay. A mouse model of diabetic retinopathy was established.

RESULTS

CircZNF532 and STAT3 were upregulated but miR-20b-5p was downregulated in the serum samples of patients with DR and HG-induced ARPE-19 cells. Elevated miR-20b-5p or CircZNF532 knockdown enhanced proliferation but reduced apoptosis and pyroptosis of ARPE-19 cells. CircZNF532 sponged miR-20b-5p and inhibited its expression. STAT3 was verified as a target of miR-20b-5p. MiR-20b-5p modulated ARPE-19 cell viability, apoptosis, and pyroptosis by targeting STAT3. Mice with STZ-induced diabetes showed elevated expressions of circZNF532 and STAT3 but decreased the level of miR-20b-5p compared with the controls. Knockdown of circZNF532 inhibited apoptosis and pyroptosis in mouse retinal tissues.

CONCLUSION

CircZNF532 knockdown rescued human RPE cells from HG-induced apoptosis and pyroptosis by regulating STAT3 via miR-20b-5p.

简介

视网膜色素上皮 (RPE) 细胞的丢失与糖尿病性视网膜病变 (DR) 的病因有关。本研究探讨了环状 RNA ZNF532 (circZNF532) 对 RPE 细胞凋亡和焦亡的影响。

材料和方法

从 DR 患者和健康志愿者采集血液样本。用人 RPE 细胞系 ARPE-19 诱导高糖 (HG)，并检测细胞活力、凋亡和焦亡。通过荧光素酶活性测定证实 miR-20b-5p 与 circZNF532 和 STAT3 的结合。建立糖尿病性视网膜病变小鼠模型。

结果

DR 患者血清样本和 HG 诱导的 ARPE-19 细胞中 circZNF532 和 STAT3 上调，但 miR-20b-5p 下调。升高的 miR-20b-5p 或 CircZNF532 敲低增强了 ARPE-19 细胞的增殖，但降低了凋亡和焦亡。CircZNF532 海绵 miR-20b-5p 并抑制其表达。STAT3 被验证为 miR-20b-5p 的靶标。miR-20b-5p 通过靶向 STAT3 调节 ARPE-19 细胞活力、凋亡和焦亡。与对照组相比，STZ 诱导糖尿病小鼠显示 circZNF532 和 STAT3 的表达升高，但 miR-20b-5p 的水平降低。circZNF532 的敲低抑制了小鼠视网膜组织中的凋亡和焦亡。