Melatonin Attenuates Diabetic Retinopathy by Regulating EndMT of Retinal Vascular Endothelial Cells via Inhibiting the HDAC7/FOXO1/ZEB1 Axis

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2024-09-19 DOI:10.1111/jpi.13008
Jiayi Ning, Minghong Pan, Hanyi Yang, Zhaoyang Wang, Xiaolan Wang, Kai Guo, Yingtong Feng, Tingke Xie, Yixuan Chen, Chengming Chen, Sida Liu, Yimeng Zhang, Yuanyong Wang, Xiaolong Yan, Jing Han
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Abstract

Diabetic retinopathy (DR) is characterized as a microvascular disease. Nonproliferative diabetic retinopathy (NPDR) presents with alterations in retinal blood flow and vascular permeability, thickening of the basement membrane, loss of pericytes, and formation of acellular capillaries. Endothelial–mesenchymal transition (EndMT) of retinal microvessels may play a critical role in advancing NPDR. Melatonin, a hormone primarily secreted by the pineal gland, is a promising therapeutic for DR. This study explored the EndMT in retinal microvessels of NPDR and its related mechanisms. The effect of melatonin on the retina of diabetic rats was evaluated by electroretinogram (ERG) and histopathologic slide staining. Furthermore, the effect of melatonin on human retinal microvascular endothelial cells (HRMECs) was detected by EdU incorporation assay, scratch assay, transwell assay, and tube formation test. Techniques such as RNA-sequencing, overexpression or knockdown of target genes, extraction of cytoplasmic and nuclear protein, co-immunoprecipitation (co-IP), and multiplex immunofluorescence facilitated the exploration of the mechanisms involved. Our findings reveal, for the first time, that melatonin attenuates diabetic retinopathy by regulating EndMT of retinal vascular endothelial cells via inhibiting the HDAC7/FOXO1/ZEB1 axis. Collectively, these results suggest that melatonin holds potential as a therapeutic strategy to reduce retinal vascular damage and protect vision in NPDR.

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褪黑激素通过抑制 HDAC7/FOXO1/ZEB1 轴调节视网膜血管内皮细胞的内切酶抑制糖尿病视网膜病变
糖尿病视网膜病变(DR)是一种微血管疾病。非增殖性糖尿病视网膜病变(NPDR)表现为视网膜血流和血管通透性的改变、基底膜增厚、周细胞丢失以及无细胞毛细血管的形成。视网膜微血管的内皮-间质转化(EndMT)可能在促进 NPDR 的发展中起着至关重要的作用。褪黑激素是一种主要由松果体分泌的激素,是一种很有前景的 DR 治疗药物。本研究探讨了 NPDR 视网膜微血管的 EndMT 及其相关机制。通过视网膜电图(ERG)和组织病理学切片染色评估了褪黑素对糖尿病大鼠视网膜的影响。此外,褪黑素对人视网膜微血管内皮细胞(HRMECs)的影响还通过EdU掺入试验、划痕试验、transwell试验和成管试验进行了检测。RNA测序、过表达或敲除靶基因、提取细胞质和细胞核蛋白、共免疫沉淀(co-IP)和多重免疫荧光等技术促进了对相关机制的探索。我们的研究结果首次揭示了褪黑激素通过抑制 HDAC7/FOXO1/ZEB1 轴来调节视网膜血管内皮细胞的 EndMT,从而减轻糖尿病视网膜病变。总之,这些结果表明,褪黑激素有可能作为一种治疗策略,减少NPDR患者的视网膜血管损伤并保护视力。
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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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