Epigenetic mechanisms in the pathogenesis of diabetic foot ulcers

Rafehi, Haloom; El‐Osta, Assam; Karagiannis, Tom C.

doi:10.1016/j.jdiacomp.2012.05.015

Cited by 32 publications

(41 citation statements)

References 97 publications

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“…This is the first report of a comprehensive DNA methylation analysis at the global and genome-wide levels using patient-derived fibroblasts within the context of diabetic wound healing. Identification of a persistent diabetic wound healing-related epigenotype in a cohort of patient fibroblasts contributes to a growing literature demonstrating that epigenetically-driven, metabolic memory directs cellular phenotypes that lead to complications associated with diabetes, 1,2,6,8,9,14,30 adding further urgency to the need for strict glycemic control in diabetic therapy.…”

Section: Discussionmentioning

confidence: 99%

“…2 Collectively, these studies have demonstrated gene expression and epigenetic profiles that are enriched in diabetes-relevant pathways, including metabolism and inflammation, and correlated with impaired cellular function and clinical complications. While a role for metabolic memory in diabetic complications has been studied in numerous cell types, including vascular smooth muscle cells, 6,12 endothelial cells, 8 glomerular mesangial cells, 10 and retinal cells, 11 no previous studies 14 have focused on the role of epigenetic metabolic memory in establishing a diabetic phenotype specifically in fibroblasts derived from chronic, non-healing diabetic foot ulcers (DFUs).…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide DNA methylation analysis identifies a metabolic memory profile in patient-derived diabetic foot ulcer fibroblasts

et al. 2014

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Diabetic foot ulcers (DFUs) are a serious complication of diabetes. Previous exposure to hyperglycemic conditions accelerates a decline in cellular function through metabolic memory despite normalization of glycemic control. Persistent, hyperglycemia-induced epigenetic patterns are considered a central mechanism that activates metabolic memory; however, this has not been investigated in patient-derived fibroblasts from DFUs. We generated a cohort of patient-derived lines from DFU fibroblasts (DFUF), and site-and age-matched diabetic foot fibroblasts (DFF) and nondiabetic foot fibroblasts (NFF) to investigate global and genome-wide DNA methylation patterns using liquid chromatography/mass spectrometry and the Illumina Infinium HumanMethylation450K array. DFFs and DFUFs demonstrated significantly lower global DNA methylation compared to NFFs (p D 0.03). Hierarchical clustering of differentially methylated probes (DMPs, p D 0.05) showed that DFFs and DFUFs cluster together and separately from NFFs. Twenty-five percent of the same probes were identified as DMPs when individually comparing DFF and DFUF to NFF. Functional annotation identified enrichment of DMPs associated with genes critical to wound repair, including angiogenesis (p D 0.07) and extracellular matrix assembly (p D 0.035). Identification of sustained DNA methylation patterns in patient-derived fibroblasts after prolonged passage in normoglycemic conditions demonstrates persistent metabolic memory. These findings suggest that epigenetic-related metabolic memory may also underlie differences in wound healing phenotypes and can potentially identify therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-wide DNA methylation analysis identifies a metabolic memory profile in patient-derived diabetic foot ulcer fibroblasts

et al. 2014

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“…Lebih lanjut neuropathy kemudian menyebabkan gangguan mekanisme waspada dari penderita terhadap benda yang berbahaya bagi integritas kulit atau jaringan di bawahnya. Hal ini ditandai dengan terbentuknya calus pada kaki penderita DM lama (Perez-Zabala et al 2016;Rafehi et al 2012).…”

Section: Pendahuluanunclassified

“…AGE ini akan bersirkulasi dalam darah dan menarik sekresi sitokin. Adanya sitokin ini yang kemudian memicu terjadinya gangguan vaskular melalui penurunan sintesis nitrit oksida, disfungsi endotel, dan menghambat komposisi matriks ekstraseluler (Perez-Zabala et al 2016;Rafehi et al 2012).…”

Section: Pendahuluanunclassified

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Profil Koagulasi Pasien Penderita Diabetes Mellitus Di Rs X, Kebumen, Jawa Tengah

Rahayu¹,

Arjana²,

Juwariyah³

et al. 2017

Biomedika

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Approaches to Control and Monitor Protease Levels in Chronic Wounds

Kolahreez,

Ghasemi‐Mobarakeh,

Liebner

et al. 2024

Advanced Therapeutics

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Some wounds do not follow the typical healing trajectory and show very little, if any, progress. They dreadfully threaten the patients' quality of life and may even lead to limb amputation and death. Several interrelated systemic and local factors may cause a delay in wound healing. The microenvironment of these wounds could be different from wounds that heal spontaneously or with standard treatment. As discussed in the present work, proteases’ levels or activity could be elevated in some cases of chronic ulcers; infection could aggravate the situation. A detailed overview of the proteases’ effect on wound healing is presented in this paper. Assuming untimely or irregularly excessive proteolytic activity plays a pathological role, some researchers targeted attenuation of protease level as a strategy to promote healing. This could be done via different approaches, including physical removal, inhibiting their activity, and controlling their expression directly through gene silencing or indirectly, for instance, by resolving infection. Apart from targeting protease modulation as a therapeutic strategy, many studies have examined the protease state to gain insights into the underlying mechanisms by which a remedy, dressing, or specific therapy has affected the healing process. This article aims to provide an overview of the studies in these two categories. Of course, various proteases are involved in the healing process, but in each study, usually, only one or some of them were investigated; matrix metalloproteinase‐2 (MMP‐2), MMP‐9, and human neutrophil elastase (HNE) are among them. Furthermore, in some cases, cumulative proteolytic activity has been evaluated in terms of gelatinolytic, collagenolytic, or caseinolytic activity, which is also absolutely beneficial. Some research groups have considered the potential of proteases as a diagnostic or prognostic biomarker and have tried to develop some sensors or indicators; this topic has also been covered in the present work.This article is protected by copyright. All rights reserved

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Epigenetic mechanisms in the pathogenesis of diabetic foot ulcers

Cited by 32 publications

References 97 publications

Genome-wide DNA methylation analysis identifies a metabolic memory profile in patient-derived diabetic foot ulcer fibroblasts

Genome-wide DNA methylation analysis identifies a metabolic memory profile in patient-derived diabetic foot ulcer fibroblasts

Profil Koagulasi Pasien Penderita Diabetes Mellitus Di Rs X, Kebumen, Jawa Tengah

Approaches to Control and Monitor Protease Levels in Chronic Wounds

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