HuD和α -结晶蛋白A轴保护早期糖尿病的神经视网膜细胞。

IF 3.7 2区 生物学 Q3 CELL BIOLOGY
Chongtae Kim, Subeen Oh, Young-Hoon Park
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引用次数: 0

摘要

糖尿病视网膜病变(DR)是糖尿病常见的微血管并发症;然而,在没有dr症状的糖尿病患者中也可以观察到神经视网膜变性。在糖尿病出现血管并发症之前,导致神经视网膜细胞丢失的机制尚不清楚。在这项研究中,我们研究了神经元rna结合蛋白HuD作为糖尿病早期神经视网膜变性的一种新的调节因子。我们检测了HuD和α -晶体蛋白A (CRYAA)在视网膜神经节细胞层的表达。在链脲佐菌素诱导的糖尿病大鼠视网膜和高糖处理的神经视网膜细胞(R-28)中,HuD和CRYAA均下调。Cryaa mRNA被鉴定为HuD的一个新的靶转录物,我们证明HuD通过结合其3'-非翻译区来调节Cryaa mRNA的转录后表达。沉默和过表达HuD可正向调节Cryaa mRNA和蛋白的表达。我们证明,在高血糖状态下,R-28细胞中炎症细胞因子如TNFα、IL-1β和IL-6的增加是CRYAA和HuD水平的结果。沉默HuD和CRYAA可增强高糖诱导的R-28细胞死亡,而它们的过表达可减轻这种作用。HuD转录后调控CRYAA表达,影响糖尿病患者神经视网膜细胞的功能和活力。我们的研究结果表明,HuD/CRYAA轴在神经视网膜细胞中起着至关重要的作用,并有可能作为糖尿病神经视网膜变性的预后因素和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HuD and alpha-crystallin A axis protects neuro-retinal cells in early diabetes.

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes; however, neuro-retinal degeneration is also observed in patients with diabetes without signs of DR. The mechanisms leading to neuro-retinal cell loss before vascular complications manifest in diabetes remain poorly understood. In this study, we investigated the neuronal RNA-binding protein HuD as a novel regulator of neuro-retinal degeneration in the early stage of diabetes. We determined the expression of HuD and alpha-crystallin A (CRYAA) in the retinal ganglion cell layer. HuD and CRYAA were down-regulated in the retinas of streptozotocin-induced diabetic rats and in neuro-retinal cells (R-28) treated with high glucose. Cryaa mRNA was identified as a novel target transcript of HuD, and we demonstrated that HuD post-transcriptionally regulates the expression of Cryaa mRNA by binding to its 3'-untranslated region. Silencing and overexpression of HuD positively regulated the expressions of Cryaa mRNA and protein. We demonstrated that the increase in inflammatory cytokines such as TNFα, IL-1β, and IL-6 in R-28 cells under hyperglycemic conditions was a result of both CRYAA and HuD levels. Silencing HuD and CRYAA enhanced high glucose-induced R-28 cell death, whereas their overexpression alleviated this effect. HuD post-transcriptionally regulates CRYAA expression, influencing the function and viability of neuro-retinal cells under diabetic conditions. Our results suggest that the HuD/CRYAA axis plays a crucial role in neuro-retinal cells and has the potential to serve as a prognostic factor and therapeutic target for diabetic neuro-retinal degeneration.

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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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