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Understanding molecular mechanisms and miRNA-based targets in diabetes foot ulcers

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Abstract

In today’s culture, obesity and overweight are serious issues that have an impact on how quickly diabetes develops and how it causes complications. For the development of more effective therapies, it is crucial to understand the molecular mechanisms underlying the chronic problems of diabetes. The most prominent effects of diabetes are microvascular abnormalities such as retinopathy, nephropathy, and neuropathy, especially diabetes foot ulcers, as well as macrovascular abnormalities such as heart disease and atherosclerosis. MicroRNAs (miRNAs), which are highly conserved endogenous short non-coding RNA molecules, have been implicated in several physiological functions recently, including the earliest stages of the disease. By binding to particular messenger RNAs (mRNAs), which cause mRNA degradation, translation inhibition, or even gene activation, it primarily regulates posttranscriptional gene expression. These molecules exhibit considerable potential as diagnostic biomarkers for disease and are interesting treatment targets. This review will provide an overview of the latest findings on the key functions that miRNAs role in diabetes and its complications, with an emphasis on the various stages of diabetic wound healing.

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Abbreviations

DFU:

Diabetes foot ulcer

MMP:

Metalloproteinase

ECM:

Extracellular matrix

VEGF:

Vascular endothelial growth factor

DN:

Diabetes neuropathy

PDGF:

Platelet derived growth factor

EC  :

Extracellular

5-HT:

5-Hydroxytryptamine

WBC:

White blood cells

RBC:

Red blood cells

HMGB-1:

High mobility group box-1

TLR:

Toll-like receptor

NFKB:

Nuclear factor kappa-light-chain-enhancer of activated B-cells

IRAK-1:

Interleukin-1 receptor-associated kinase 1

TRAF6:

Tumor necrosis factor (TNF) receptor-associated factor-6

HIC-5:

Hydrogen peroxideinducible clone 5

HIC-5  :

Hydrogen peroxideinducible clone 5

PKC:

Protein kinase-C

T2D  :

Type 2 diabetess

DM:

Diabetes Mellitus

miRNA:

MacroRNA

mRNA  :

Messenger RNAs

AGE:

Advanced glycation end products

USD:

United States dollars

US:

United States

NGF:

Nerve growth factor

FGF2:

Fibroblast growth factor-2

DPN:

Diabetes peripheral neuropathy

DN:

Diabetes neuropathy

PVD  :

Peripheral vascular disease

PAD:

Peripheral artery disease

MRSA:

Methicillin-resistant staphylococcus aureus

M1:

Pro-inflammatory phenotype

M2:

Anti-inflammatory phenotype

FGF:

Fibroblast growth factor

DNA:

Deoxyribonucleic acid

tRNA:

Transfer RNA

rRNA:

Ribosomal RNA

RNAi  :

RNA inference

NETs:

Neutrophil extracellular trap

TIMPs:

tissue inhibitors of metalloproteinases

GTPase:

GTP-binding proteins

SHIP1:

SH-2 containing inositol 5’ polyphosphate 1

FIZZ1:

Inflammatory zone protein

BCL-6:

B-cell lymphoma 6

STAT4:

Signal transducer and activator of transcription 4

IFN- γ:

Interferon-gamma

NK Cells:

Natural killer cells

PDCD-4:

Programmed Cell Death 4

ZO-1:

Zonula occludens-1

DAXX:

Death-domain associated protein

GLUT-1:

Glucose transporter 1

PTEN:

 Phosphatase and tensin homolog

TSP-1:

Thrombospondin 1

TSP-2:

Thrombospondin-2

MTOR:

Mammalian target of rapamycin

IGF1R:

Insulin-like growth factor 1 receptor

SIRT-1:

Sirtuin (silent mating type information regulation 2 homolog) 1

SMAD-4:

 SMAD family member 4

E2F3:

E2F Transcription Factor 3

COL3A1:

Collagen, type III, alpha 1

COL4A1:

Collagen, type IV, alpha 1

COL4A2:

Collagen, type IV, alpha 2

COL5A1:

Collagen, type V, alpha 1

COLIA1:

Collagen, type I, alpha 1

ZEB2:

Zinc Finger E-Box Binding Homeobox 2

ZEB1:

Zinc Finger E-Box Binding Homeobox 1

HBEGF:

Heparin-binding EGF-like growth factor

qPCR:

Quantitative polymerase chain reaction

MSC:

Mesenchymal stem cells

HBOT:

Hyperbaric oxygen therapy

NPWT:

Negative pressure wound therapy

ESWT:

Extracorporeal shock wave therapy

ROS:

Reactive oxygen species

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

IL-8:

Interleukin-8

IL-10:

Interlukin-10

IGF-1:

Insulin-like growth factor-1

TNF-α:

Tumour necrosis factor

TGF-β:

Transforming growth factor beta

siRNA:

Short interfering RNA or Silencing RNA

snoRNA  :

Small nucleolar RNA

RNA:

Ribonucleic acid

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Acknowledgements

The Department of Science and Technology, Ministry of Science and Technology (DST), Government of India, as well as the Department of Pharmaceuticals (DoP), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India, are all acknowledged by the authors for providing the necessary facilities, infrastructure, and financial support.

Funding

Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers, Govt. of India, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad, India, and also acknowledge the Department of Science and Technology, Ministry of Science and Technology (DST), Govt of India.

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  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Hyderabad, Telangana, 500037, India

    Urati Anuradha & Dharmendra Kumar Khatri

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Hyderabad, Telangana , 500037, India

    Neelesh Kumar Mehra

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Anuradha, U., Mehra, N.K. & Khatri, D.K. Understanding molecular mechanisms and miRNA-based targets in diabetes foot ulcers. Mol Biol Rep 51, 82 (2024). https://doi.org/10.1007/s11033-023-09074-0

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