LLLT-ADSCs Curtail the Progression of Keloid Through Exosomal miR-26a-5p Downregulating Jag/Notch Pathway.

BACKGROUND

Adipose-derived stem cells treated with low-level laser light (LLLT-ADSCs) demonstrate an inhibitory effect on keloid scars, although the underlying molecular mechanisms remain largely unknown. This study aims to elucidate these mechanisms.

METHODS

We investigated the morphology, quantity, and microRNA (miRNA) expression profiles of exosomes derived from LLLT-ADSCs compared to those from untreated ADSCs. Notably, hsa-miR-26a-5p was found to be highly expressed in exosomes from LLLT-ADSCs. We examined its impact on the proliferation, migration, and invasion of keloid fibroblasts (KFs) by modulating its expression levels in these cells. A dual-luciferase reporter assay was utilized to confirm the interaction between hsa-miR-26a-5p and the Jagged-1/Notch signaling pathway.

RESULTS

Significant variations were observed in the exosomal contents between LLLT-ADSCs and ADSCs. Enhanced expression of hsa-miR-26a-5p was associated with reduced proliferation, migration, and invasion of KFs, along with diminished expression of Jagged-1 and NICD proteins. Conversely, suppression of hsa-miR-26a-5p expression reversed these effects. The dual-luciferase reporter system demonstrated that modifications in the binding sites of Jag-1 significantly mitigated the downregulation of Jag-1 expression induced by miRNA interaction.

CONCLUSIONS

LLLT-ADSCs can produce and deliver hsa-miR-26a-5p via exosomes to suppress the Jagged-1/Notch pathway activation in KFs, thereby effectively preventing the progression of keloid scars. This mechanism presents a novel therapeutic strategy for managing keloid scars.