Epigenetic regulation of Nrf2-Mediated angiogenesis in diabetic foot ulcer progression: Role of histone deacetylases

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kannan Harithpriya , Ravichandran Jayasuriya , K.L. Milan , Udyama Juttada , Satyavani Kumpatla , Vijay Viswanathan , Kunka Mohanram Ramkumar
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引用次数: 0

Abstract

Nuclear factor E2-related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates proangiogenic mediators, and antioxidant and detoxification enzymes. However, hitherto its regulation in the progression of DFU was poorly examined. The regulation of Nrf2 has been reported to be affected by various factors, including histone deacetylase (HDACs) and DNA methylation. The present study aimed to profile all classes of HDACs and correlate them with Nrf2 and angiogenic markers in the tissue biopsies of different grades of DFU patients (n = 20 in each grade). The gene expression profile of Nrf2 and its downstream targets, angiogenic markers, and all classes of HDACs were assessed using qPCR. Spearman's correlation was performed to analyze the correlation of HDACs with Nrf2 and its downstream targets along with angiogenic markers. We observed a progressive decrease in the gene expression of Nrf2 and angiogenic markers such as VEGF, HIF-1α, and SDF-1α and also an increase in the TSP-2 expression in different grades of DFU. In parallel, a significant downregulation of HDAC2/8 and SIRT1/2/4 has been observed in various grades of DFU subjects. On the other hand, HDAC1/3/4/11 and SIRT3/5/6/7 showed upregulation in different grades of DFU and the maximum increase was observed in Grade 3 patients. A significant negative correlation between Nrf2 and HDAC4, angiogenic markers, and HDAC4 suggested the pivotal role of the HDAC4-regulated Nrf2-mediated angiogenesis among DFU subjects. We have generated a first line of evidence on the epigenetic regulation of Nrf2 and its correlation with angiogenesis in the progression of diabetic foot ulcers.

Abstract Image

糖尿病足溃疡进展中 Nrf2 介导的血管生成的表观遗传调控:组蛋白去乙酰化酶的作用。
核因子E2相关因子2(Nrf2)是一种对氧化还原反应敏感的转录因子,可调节促血管生成介质以及抗氧化和解毒酶。然而,迄今为止,人们对其在 DFU 进展过程中的调控作用研究甚少。据报道,Nrf2的调控受多种因素的影响,包括组蛋白去乙酰化酶(HDACs)和DNA甲基化。本研究旨在分析不同等级DFU患者(每个等级20人)组织活检样本中的各类HDACs,并将其与Nrf2和血管生成标志物相关联。使用 qPCR 评估了 Nrf2 及其下游靶标、血管生成标记物和各类 HDAC 的基因表达谱。斯皮尔曼相关性分析了 HDAC 与 Nrf2 及其下游靶点和血管生成标志物的相关性。我们观察到,在不同等级的 DFU 中,Nrf2 和血管生成标志物(如血管内皮生长因子、HIF-1α 和 SDF-1α)的基因表达逐渐减少,TSP-2 的表达也有所增加。与此同时,在不同等级的 DFU 受试者中观察到 HDAC2/8 和 SIRT1/2/4 的表达明显下调。另一方面,HDAC1/3/4/11和SIRT3/5/6/7在不同等级的DFU中表现出上调,在3级患者中增幅最大。Nrf2和HDAC4、血管生成标志物与HDAC4之间的明显负相关表明,HDAC4调控的Nrf2介导的血管生成在DFU受试者中起着关键作用。我们为 Nrf2 的表观遗传调控及其与血管生成在糖尿病足溃疡进展中的相关性提供了第一手证据。
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来源期刊
Archives of biochemistry and biophysics
Archives of biochemistry and biophysics 生物-生化与分子生物学
CiteScore
7.40
自引率
0.00%
发文量
245
审稿时长
26 days
期刊介绍: Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.
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