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Review
. 2023 Mar 20:10:1140979.
doi: 10.3389/fmed.2023.1140979. eCollection 2023.

Effects of microRNAs on angiogenesis in diabetic wounds

Bailey D Lyttle  1 , Alyssa E Vaughn  1 , James R Bardill  1 , Anisha Apte  2 , Lauren T Gallagher  1 , Carlos Zgheib  2 , Kenneth W Liechty  2
Affiliations
Review

Effects of microRNAs on angiogenesis in diabetic wounds

Bailey D Lyttle et al. Front Med (Lausanne). .

Abstract

Diabetes mellitus is a morbid condition affecting a growing number of the world population, and approximately one third of diabetic patients are afflicted with diabetic foot ulcers (DFU), which are chronic non-healing wounds that frequently progress to require amputation. The treatments currently used for DFU focus on reducing pressure on the wound, staving off infection, and maintaining a moist environment, but the impaired wound healing that occurs in diabetes is a constant obstacle that must be faced. Aberrant angiogenesis is a major contributor to poor wound healing in diabetes and surgical intervention is often necessary to establish peripheral blood flow necessary for healing wounds. Over recent years, microRNAs (miRNAs) have been implicated in the dysregulation of angiogenesis in multiple pathologies including diabetes. This review explores the pathways of angiogenesis that become dysregulated in diabetes, focusing on miRNAs that have been identified and the mechanisms by which they affect angiogenesis.

Keywords: angiogenesis; chronic wounds; diabetes mellitus; diabetic foot ulcers; microRNA; wound healing.

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Conflict of interest statement

CZ was Chief Scientific Officer of Ceria Therapeutics. KL was President of Ceria Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mechanisms of angiogenesis affected by microRNAs. Endothelial cells line blood vessel walls and are the main cells affected by processes of angiogenesis. Circulating pro-angiogenic factors (green arrow, bold outline), anti-angiogenic factors (red arrow, no outline), and mixed factors (yellow arrow, dashed outline) all interact with endothelial cells and influence intracellular signaling including the extracellular signal-regulated kinases-mitogen activated protein kinases (ERK-MAPK) and phosphatidylinositol 3-kinase (PI3K)-Protein Kinase B (AKT) pathways, which ultimately regulate angiogenic sprouting and endothelial migration and proliferation. Intracellular protein Sprouty (Spry) inhibits ERK-MAPK signaling to downregulate angiogenesis (red flathead arrow). MicroRNAs (MiRNAs) influence angiogenesis throughout the cellular pathways—pro-angiomiRs are denoted in green plain text and anti-angiomiRs in red italicized text.
See this image and copyright information in PMC

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