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靶向糖尿病足溃疡中的 DNA 甲基化和去甲基化。

Targeting DNA methylation and demethylation in diabetic foot ulcers.

机构信息

Key Lab of the Basic Pharmacology of the Ministry of Education, Zunyi Medical University, Zunyi 563006, China; Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China; College of Pharmacy, Zunyi Medical University, Zunyi 563006, China.

College of Pharmacy, Zunyi Medical University, Zunyi 563006, China.

出版信息

J Adv Res. 2023 Dec;54:119-131. doi: 10.1016/j.jare.2023.01.009. Epub 2023 Jan 25.

Abstract

BACKGROUND

Poor wound healing is a significant complication of diabetes, which is commonly caused by neuropathy, trauma, deformities, plantar hypertension and peripheral arterial disease. Diabetic foot ulcers (DFU) are difficult to heal, which makes patients susceptible to infections and can ultimately conduce to limb amputation or even death in severe cases. An increasing number of studies have found that epigenetic alterations are strongly associated with poor wound healing in diabetes.

AIM OF REVIEW

This work provides significant insights into the development of therapeutics for improving chronic diabetic wound healing, particularly by targeting and regulating DNA methylation and demethylation in DFU. Key scientific concepts of review: DNA methylation and demethylation play an important part in diabetic wound healing, via regulating corresponding signaling pathways in different breeds of cells, including macrophages, vascular endothelial cells and keratinocytes. In this review, we describe the four main phases of wound healing and their abnormality in diabetic patients. Furthermore, we provided an in-depth summary and discussion on how DNA methylation and demethylation regulate diabetic wound healing in different types of cells; and gave a brief summary on recent advances in applying cellular reprogramming techniques for improving diabetic wound healing.

摘要

背景

伤口愈合不良是糖尿病的一个严重并发症,通常由神经病变、创伤、畸形、足底高压和外周动脉疾病引起。糖尿病足溃疡(DFU)难以愈合,使患者容易感染,在严重情况下最终可导致截肢甚至死亡。越来越多的研究发现,表观遗传改变与糖尿病中伤口愈合不良密切相关。

综述目的

本研究深入探讨了通过靶向和调节 DFU 中的 DNA 甲基化和去甲基化来改善慢性糖尿病性伤口愈合的治疗方法。综述的关键科学概念:DNA 甲基化和去甲基化通过调节不同类型细胞(包括巨噬细胞、血管内皮细胞和角质形成细胞)中的相应信号通路,在糖尿病伤口愈合中起着重要作用。在本综述中,我们描述了伤口愈合的四个主要阶段及其在糖尿病患者中的异常情况。此外,我们深入总结和讨论了 DNA 甲基化和去甲基化如何调节不同类型细胞中的糖尿病伤口愈合,并简要总结了应用细胞重编程技术改善糖尿病性伤口愈合的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/046b/10703625/cb5018254b5c/ga1.jpg

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