Epidermal Stem Cell Derived Exosomes-induced Dedifferentiation of Myofibroblasts Inhibits Scarring Via the MiR-203a-3p/PIK3CA Axis

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Date 2025 Jan 29

PMID 39881312

Authors

Shixin Zhao

Haoran Kong

Dahu Qi

Yushuang Qiao

Yu Li

Zhiming Cao

Hanwen Wang

Xuefeng He

Hengdeng Liu

Hao Yang

Suyue Gao

Tao Liu

Julin Xie

Affiliations

Soon will be listed here.

Abstract

Hypertrophic scar (HS) is a common fibroproliferative disorders with no fully effective treatments. The conversion of fibroblasts to myofibroblasts is known to play a critical role in HS formation, making it essential to identify molecules that promote myofibroblast dedifferentiation and to elucidate their underlying mechanisms. In this study, we used comparative transcriptomics and single-cell sequencing to identify key molecules and pathways that mediate fibrosis and myofibroblast transdifferentiation. Epidermal stem cell-derived extracellular vesicles (EpiSC-EVs) were isolated via ultracentrifugation and filtration, followed by miRNA sequencing to identify miRNAs targeting key molecules. After in vitro and in vivo treatment with EpiSC-EVs, we assessed antifibrotic effects through scratch assays, collagen contraction assays, Western blotting, and immunofluorescence. Transcriptomic sequencing and rescue experiments were used to investigate the molecular mechanism by which miR-203a-3p in EpiSC-EVs induces myofibroblast dedifferentiation. Our results indicate that PIK3CA is overexpressed in HS tissues and positively correlates with fibrosis. EpiSC-EVs were absorbed by scar-derived fibroblasts, promoting dedifferentiation from myofibroblasts to quiescent fibroblasts. Mechanistically, miR-203a-3p in EpiSC-EVs plays an essential role in inhibiting PIK3CA expression and PI3K/AKT/mTOR pathway hyperactivation, thereby reducing scar formation. In vivo studies confirmed that EpiSC-EVs attenuate excessive scarring through the miR-203a-3p/PIK3CA axis, suggesting EpiSC-EVs as a promising therapeutic approach for HS.

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