MiR-195-5p and miR-205-5p in extracellular vesicles isolated from diabetic foot ulcer wound fluid decrease...

Area of Science:

• Biomedical research
• Molecular biology
• Wound healing research

Background:

• Diabetic foot ulcers exhibit poor healing, primarily due to impaired angiogenesis.
• Extracellular vesicles (EVs) are implicated in intercellular communication and tissue repair.
• Understanding the role of wound fluid EVs in diabetic foot ulcer pathogenesis is crucial.

Purpose of the Study:

• To investigate the impact of extracellular vesicles (EVs) from diabetic foot ulcer wound fluid on angiogenesis.
• To identify the molecular mechanisms by which these EVs affect new vessel formation and wound healing.

Main Methods:

• Isolation of EVs from diabetic foot ulcer wound fluid (DF-EVs).
• Assessment of DF-EVs' effect on human umbilical vein endothelial cells (HUVECs) and wound healing models.
• Microarray analysis and qRT-PCR to identify differentially expressed microRNAs (miRNAs) in DF-EVs.
• Dual-luciferase reporter assays and overexpression experiments to validate miRNA targets.

Main Results:

• DF-EVs demonstrated an inhibitory effect on HUVEC proliferation and migration, crucial for angiogenesis.
• Microarray and qRT-PCR identified miR-195-5p and miR-205-5p as upregulated in DF-EVs.
• These miRNAs directly target the 3' UTR of vascular endothelial growth factor A (VEGFA) mRNA, reducing its expression.
• Inhibition of VEGFA by DF-EVs-derived miRNAs negatively impacted angiogenesis and wound healing.

Conclusions:

• Extracellular vesicles in diabetic foot ulcer wound fluid carry anti-angiogenic miRNAs (miR-195-5p, miR-205-5p).
• These miRNAs inhibit angiogenesis and impair wound healing by downregulating VEGFA.
• DF-EVs represent a potential therapeutic target for improving diabetic foot ulcer healing.