Downregulated HDAC3 or up-regulated microRNA-296-5p alleviates diabetic retinopathy in a mouse model

Regenerative Therapy

Peng Yu¹  Shuai Wu²  Songtian Che³ 

[1] Ocular Plastic Surgery, the Second Hospital of Jilin University, No. 4026, Yatai Street, Changchun 130041, Jilin, People's Republic of China;;Department Orbital Diseases &Department of Ocular Fundus Disease, the Second Hospital of Jilin University, No. 4026, Yatai Street, Changchun 130041, Jilin, People's Republic of China;

关键词: Diabetic retinopathy;    Histone deacetylase 3;    MicroRNA-296-5p;    G protein subunit alpha i2;    Apoptosis;    Retinal ganglion cells;   

DOI  :  

来源: DOAJ

【 摘 要 】

Objective: 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. Methods: 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. Results: 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. Conclusion: Depleting HDAC3 or restoring miR-296-5p suppresses apoptosis of retinal ganglion cells of DR mice via down-regulating GNAI2.

【 授权许可】

Unknown