Che Songtian, Wu Shuai, Yu Peng
Department of Ocular Fundus Disease, the Second Hospital of Jilin University, No. 4026, Yatai Street, Changchun 130041, Jilin, People's Republic of China.
Department Orbital Diseases & Ocular Plastic Surgery, the Second Hospital of Jilin University, No. 4026, Yatai Street, Changchun 130041, Jilin, People's Republic of China.
Regen Ther. 2022 May 18;21:1-8. doi: 10.1016/j.reth.2022.04.002. eCollection 2022 Dec.
It has been demonstrated the efficacy of histone deacetylase 3 (HDAC3) in diabetes. Nevertheless, the function of HDAC3 in diabetic retinopathy (DR) remained largely obscure. Here, we investigated the HDAC3 effects in DR mice through the microRNA (miR)-296-5p/G protein subunit alpha i2 (GNAI2) axis.
The mice diabetes model was established. HDAC3, GNAI2 and miR-296-5p levels in retina tissues of DR mice were evaluated. The weight, blood glucose, Evans blue leakage in DR mice, apoptosis of retinal ganglion cells, vascular endothelial growth factor (VEGF) and malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity in DR mice were detected after miR-296-5p elevation or HDAC3 depletion. The relations among HDAC3, miR-296-5p and GNAI2 were validated.
HDAC3 and GNAI2 expressed at a high level while miR-296-5p expressed at a low level in retina tissues of DR mice. Restoring miR-296-5p or depleting HDAC3 reduced Evans blue leakage in DR mice, attenuated apoptosis of retinal ganglion cells, reduced VEGF and MDA, and enhanced SOD activity in serum and retinal tissues of DR mice. HDAC3 repressed miR-296-5p expression by binding to its promoter region, thereby enhancing GNAI2 expression.
Depleting HDAC3 or restoring miR-296-5p suppresses apoptosis of retinal ganglion cells of DR mice via down-regulating GNAI2.
已证实组蛋白去乙酰化酶3（HDAC3）在糖尿病中具有疗效。然而，HDAC3在糖尿病视网膜病变（DR）中的功能仍不清楚。在此，我们通过微小RNA（miR）-296-5p/G蛋白亚基α i2（GNAI2）轴研究HDAC3对DR小鼠的影响。
建立小鼠糖尿病模型。评估DR小鼠视网膜组织中HDAC3、GNAI2和miR-296-5p的水平。在miR-296-5p升高或HDAC3缺失后，检测DR小鼠的体重、血糖、伊文思蓝渗漏、视网膜神经节细胞凋亡、血管内皮生长因子（VEGF）和丙二醛（MDA）含量以及超氧化物歧化酶（SOD）活性。验证HDAC3、miR-296-5p和GNAI2之间的关系。
DR小鼠视网膜组织中HDAC3和GNAI2高表达，而miR-296-5p低表达。恢复miR-296-5p或缺失HDAC3可减少DR小鼠的伊文思蓝渗漏，减轻视网膜神经节细胞凋亡，降低VEGF和MDA水平，并增强DR小鼠血清和视网膜组织中的SOD活性。HDAC3通过结合其启动子区域抑制miR-296-5p表达，从而增强GNAI2表达。
缺失HDAC3或恢复miR-296-5p可通过下调GNAI2抑制DR小鼠视网膜神经节细胞凋亡。
