Exosomal miR-767 from senescent endothelial-derived accelerating skin fibroblasts aging via inhibiting TAB1

Area of Science:

• Cell Biology
• Dermatology
• Molecular Biology

Background:

• Skin aging is a complex process influenced by microRNA regulation.
• Exosomes mediate intercellular communication and are implicated in various diseases.
• The role of vascular endothelial cell-derived exosomes in skin aging was previously unreported.

Purpose of the Study:

• To investigate the role of senescent vascular endothelial cell-derived exosomes in skin aging.
• To identify specific microRNAs involved in this process.
• To elucidate the molecular mechanisms underlying exosome-mediated skin aging.

Main Methods:

• Senescent endothelial cells and their derived exosomes were utilized.
• MicroRNA expression analysis (miR-767) in cells and exosomes.
• Skin fibroblast cultures treated with exosomes and transfected with miR-767 mimics/inhibitors.
• Double luciferase assay to confirm target gene (TAB1).
• In vivo studies using D-galactose induced aging mice and miR-767 overexpression models.
• Histological analysis (HE staining) of mouse skin.

Main Results:

• Senescent endothelial cell-derived exosomes promote skin fibroblast senescence.
• miR-767 is upregulated in senescent vascular endothelial cells, their exosomes, and in skin fibroblasts exposed to these exosomes.
• miR-767 directly targets TAB1.
• In vivo, miR-767 is upregulated, and TAB1 is downregulated in aging mouse models.
• Overexpression of miR-767 in mice leads to dermal thinning and aged appearance.

Conclusions:

• Senescent vascular endothelial cell-derived exosomes mediate miR-767, which promotes skin fibroblast aging via the exosome pathway.
• This study reveals the involvement of vascular endothelial cell-derived exosomes in skin aging.
• miR-767 and TAB1 represent potential therapeutic targets for delaying skin senescence.