BAT-derived miR-378a-3p facilitates endothelial angiogenic function and promotes wound healing

Area of Science:

• Vascular Biology
• Adipose Tissue Biology
• Extracellular Vesicles

Background:

• Interscapular brown adipose tissue (iBAT) is highly vascularized and secretes exosomes.
• Exosomes are involved in vascular remodeling and cell migration.
• The role of BAT-derived exosomes (BATexos) in peripheral vasculature is not well understood.

Purpose of the Study:

• To investigate whether BATexos modulate peripheral vasculature.
• To identify key mediators within BATexos responsible for vascular effects.
• To explore the therapeutic potential of BATexos and their cargo in tissue repair.

Main Methods:

• Administration of BATexos to assess effects on angiogenesis and vascular repair.
• Identification and functional analysis of microRNAs within BATexos, specifically miR-378a-3p.
• Inhibition of exosome secretion from BAT to evaluate impact on wound healing.
• Mechanistic studies involving target gene identification (Pten) and signaling pathway analysis (PI3K-AKT).
• In vivo studies using liposomes encapsulating miR-378 mimics in a diabetic mouse model.

Main Results:

• BATexos significantly promoted peripheral angiogenesis and vascular repair.
• miR-378a-3p, enriched in BATexos, was identified as a key mediator of endothelial cell migration and tube formation.
• Inhibition of exosome secretion from BAT impaired vascular repair and delayed wound healing.
• miR-378a-3p directly targeted Pten, activating the PI3K-AKT pathway.
• Liposomal miR-378 mimics enhanced angiogenesis and accelerated wound healing in diabetic mice.

Conclusions:

• BAT-derived miR-378a-3p is a crucial regulator of vessel regeneration and tissue repair.
• BATexos facilitate peripheral angiogenesis and vascular repair through miR-378a-3p.
• Targeting BAT-derived miR-378a-3p presents a promising therapeutic strategy for vascular complications in metabolic diseases.