Mechanistic Actions of microRNAs in Diabetic Wound Healing

Petković, Marija; Sørensen, Anja Elaine; Leal, Ermelindo C.; Carvalho, Eugénia; Dalgaard, Louise Torp

doi:10.3390/cells9102228

Cited by 48 publications

(46 citation statements)

References 240 publications

(268 reference statements)

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“…Wound healing comprises a complex and dynamic series of cellular and biochemical events which consists of the following four overlapping phases: hemostasis, inflammation, proliferation, and remodeling [ 5 , 27 , 28 , 29 ]. The hemostasis phase begins with constriction of the injured blood vessels and activation of platelets to form a fibrin clot to stop the bleeding [ 27 , 30 ].…”

Section: Diabetic Foot Infectionmentioning

confidence: 99%

“…Chronic non-healing wounds often develop in people with diabetes. If wounds do not heal within 12 weeks, they are defined as chronic wounds according to the Food and Drug Administration [ 29 , 31 , 32 ]. Furthermore, in the presence of conditions such as hyperglycemia, chronic inflammation, hypoxia, peripheral neuropathy, impaired angiogenesis, and infection the wound healing progress in diabetes can become stalled [ 31 , 32 ].…”

Section: Diabetic Foot Infectionmentioning

confidence: 99%

“…Upon injury and infection, the innate immune system is activated and leads to the production of these small molecules by different resident cells of the skin such as keratinocytes, the predominant cell type of the epidermis [ 26 , 41 , 42 , 43 ]. Indeed, pathogen-associated molecular patterns (PAMPs), such as lipoarabinomannan, lipopolysaccharides and proinflammatory cytokines, are recognized by the innate immune system, leading to the up-regulation and overexpression of AMPs to promote a fast and effective response to injury and infection [ 23 , 29 , 45 , 46 ].…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

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Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers

2021

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Diabetic foot ulcer (DFU) is a devastating complication, affecting around 15% of diabetic patients and representing a leading cause of non-traumatic amputations. Notably, the risk of mixed bacterial–fungal infection is elevated and highly associated with wound necrosis and poor clinical outcomes. However, it is often underestimated in the literature. Therefore, polymicrobial infection control must be considered for effective management of DFU. It is noteworthy that antimicrobial resistance is constantly rising overtime, therefore increasing the need for new alternatives to antibiotics and antifungals. Antimicrobial peptides (AMPs) are endogenous peptides that are naturally abundant in several organisms, such as bacteria, amphibians and mammals, particularly in the skin. These molecules have shown broad-spectrum antimicrobial activity and some of them even have wound-healing activity, establishing themselves as ideal candidates for treating multi-kingdom infected wounds. Furthermore, the role of AMPs with antifungal activity in wound management is poorly described and deserves further investigation in association with antibacterial agents, such as antibiotics and AMPs with antibacterial activity, or alternatively the application of broad-spectrum antimicrobial agents that target both aerobic and anaerobic bacteria, as well as fungi. Accordingly, the aim of this review is to unravel the molecular mechanisms by which AMPs achieve their dual antimicrobial and wound-healing properties, and to discuss how these are currently being applied as promising therapies against polymicrobial-infected chronic wounds such as DFUs.

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Section: Diabetic Foot Infectionmentioning

confidence: 99%

Section: Diabetic Foot Infectionmentioning

confidence: 99%

Section: Antimicrobial Peptidesmentioning

confidence: 99%

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Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers

2021

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“…Although various anti-ageing compounds including metformin, quercetin and even aspirin 215 have been linked to an improved "younger" chromatin architecture, further studies are needed to elucidate how these drugs target epigenetic networks to affect the cutaneous wound healing process and potentially prevent development of chronic wounds. The utilization of non-coding RNAs as therapeutic targets for wound healing disorders is also rapidly developing 60,72 ; however, caution should be taken as the pathology of impaired wound healing results from a complex aetiology and malfunction of multiple cell types, often involving more than a single non-coding RNA.…”

Section: Con Clus I On S and Future Per S Pec Tivementioning

confidence: 99%

Epigenetic regulation of cellular functions in wound healing

Pastar

Marjanovic

Stone

et al. 2021

Experimental Dermatology

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Cutaneous wound healing is a complex process involving numerous cell types to accomplish sequential, yet overlapping phases of inflammation, proliferation and tissue remodelling. 1,2 Immediately after injury, blood components are released into the wound, forming a clot which provides a matrix for the influx of inflammatory cells.The inflammatory phase is characterized by leukocyte migration to the wound. Neutrophils primarily remove bacteria, followed by monocytes which further differentiate into macrophages that exert early pro-inflammatory and late anti-inflammatory functions during the healing process. Deposition of the newly synthesized fibrin matrix and granulation tissue formation follow; these are subsequently replaced by collagen and scar tissue during the final stages of wound healing. The proliferative phase of wound healing is characterized by re-epithelialization, neovascularization and extracellular matrix deposition. 1,3 Historically, exploration of the molecular basis of wound healing has included a primary focus on its spatiotemporal regulation. Given the complexity of the wound healing process and its requirement for stringent regulation, epigenetic regulation including histone modifications and DNA methylation is highly likely to play a role. 4,5 Indeed, recent discoveries in the field of non-coding RNAs have identified roles for microRNAs (miRs), circular RNAs (circRNA) and long noncoding RNAs (lncRNA) as global gene expression regulators involved in an array of processes important for successful wound healing. [6][7][8][9] While the primary focus of previous reviews has been on the role of epigenetic modifications in acute wound healing, 4-8 herein we

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“…The ability of HDL to modulate the expression within, and secretion of, selected small non-coding microRNA sequences in cells is well established, achieving regulation of expression of networks of genes, including those involved in lipoprotein metabolism and intercellular communication [25][26][27][28]. Equally, microRNA sequences have been shown to modulate the process of wound healing [29][30][31][32], but insights into the genetic mechanism(s) by which HDL promote this process are lacking are present. In this study, we have investigated the impact of HDL on 'scratch' wound healing by keratinocytes, neonatal and adult fibroblasts, validated a microchip array screen of selected microRNA sequences altered in human dermal fibroblasts by HDL treatment, and explored the role of one sequence, hsa-miR-6727-5p, in the process of wound healing in vitro.…”

Section: Introductionmentioning

confidence: 99%

Homo Sapiens (Hsa)-microRNA (miR)-6727-5p Contributes to the Impact of High-Density Lipoproteins on Fibroblast Wound Healing In Vitro

Bastaki¹,

Tarlton²,

Lightbody³

et al. 2022

Membranes

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Chronic, non-healing wounds are a significant cause of global morbidity and mortality, and strategies to improve delayed wound closure represent an unmet clinical need. High-density lipoproteins (HDL) can enhance wound healing, but exploitation of this finding is challenging due to the complexity and instability of these heterogeneous lipoproteins. The responsiveness of primary human neonatal keratinocytes, and neonatal and human dermal fibroblasts (HDF) to HDL was confirmed by cholesterol efflux, but promotion of ‘scrape’ wound healing occurred only in primary human neonatal (HDFn) and adult fibroblasts (HDFa). Treatment of human fibroblasts with HDL induced multiple changes in the expression of small non-coding microRNA sequences, determined by microchip array, including hsa-miR-6727-5p. Intriguingly, levels of hsa-miR-6727-5p increased in HDFn, but decreased in HDFa, after exposure to HDL. Delivery of a hsa-miR-6727-5p mimic elicited repression of different target genes in HDFn (ZNF584) and HDFa (EDEM3, KRAS), and promoted wound closure in HDFn. By contrast, a hsa-miR-6727-5p inhibitor promoted wound closure in HDFa. We conclude that HDL treatment exerts distinct effects on the expression of hsa-miR-6727-5p in neonatal and adult fibroblasts, and that this is a sequence which plays differential roles in wound healing in these cell types, but cannot replicate the myriad effects of HDL.

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Mechanistic Actions of microRNAs in Diabetic Wound Healing

Cited by 48 publications

References 240 publications

Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers

Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers

Epigenetic regulation of cellular functions in wound healing

Homo Sapiens (Hsa)-microRNA (miR)-6727-5p Contributes to the Impact of High-Density Lipoproteins on Fibroblast Wound Healing In Vitro

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