Mechanism study of miR-376b-5p derived from human adipose mesenchymal stem cell exosomes inhibiting hypertrophic scars via mediating the TGF-β1/Smad pathway
10.3760/cma.j.cn431274-20250827-01101
- VernacularTitle:人脂肪间充质干细胞外泌体miR-376b-5p介导TGF-β1/Smad通路抑制增生性瘢痕的机制研究
- Author:
Ming ZHAO
1
;
Tao CAO
;
Shiqing ZHENG
;
Bo CHEN
;
Bingnan LI
;
Ke TAO
Author Information
1. 空军军医大学第一附属医院全军烧伤中心烧伤与皮肤外科，西安 710032
- Publication Type:Journal Article
- Keywords:
Hyperplastic scar;
Mesenchymal stem cell;
Exosomes;
miR-376b-5p;
TGF-β-Smad pathway
- From:
Journal of Chinese Physician
2025;27(11):1612-1618
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the molecular mechanism by which adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) inhibit hypertrophic scars (HS), and to identify the key functional miRNA and its downstream signaling pathway.Methods:A mouse model of hypertrophic scars was established by subcutaneous injection of bleomycin. The dorsal fibrotic modeling area was intervened with human ADSC-Exos (ADSC-Exos group), while the control group was injected with the same volume of PBS. HE and Masson staining were used to evaluate the morphological changes and collagen deposition of skin scar tissue in the two groups. Immunohistochemistry was performed to detect the expression of collagen 1 (Col-1) and α-smooth muscle actin (α-SMA). Western blot was used to determine the expression levels of key proteins in the transforming growth factor-β1 (TGF-β1)/Smad pathway (p-Smad2/3, Smad2/3). RNA sequencing datasets from the public database (GEO) were downloaded to analyze and screen differentially expressed miRNAs after ADSC-Exos treatment. In vitro cultured human hypertrophic scar fibroblasts (HSF) were transfected with miR-376b-5p mimic or inhibitor on the basis of ADSC-Exos treatment, and the expression of fibrosis markers (Col-1, α-SMA) as well as p-Smad2/3 and Smad2/3 was detected.Results:In vivo experiments showed that ADSC-Exos treatment significantly improved the fibrotic phenotype of mouse scar tissue, reduced the expression of Col-1 and α-SMA, and decreased the phosphorylation of Smad2/3 protein. Bioinformatics analysis revealed that miR-376b-5p was one of the most significantly upregulated miRNAs after ADSC-Exos treatment. In vitro experiments confirmed that overexpression of miR-376b-5p could mimic the antifibrotic effect of ADSC-Exos, significantly inhibit the expression of Col-1 and α-SMA in HSF, and reduce the phosphorylation level of Smad2/3. Specific inhibition of miR-376b-5p could effectively reverse the inhibitory effect of ADSC-Exos on the fibrotic phenotype of HSF and the phosphorylation of Smad2/3.Conclusions:This study reveals that ADSC-Exos exert their antifibrotic effect by mediating miR-376b-5p to target and inhibit the activation of the TGF-β1/Smad signaling pathway. miR-376b-5p is a key functional molecule in ADSC-Exos, and this finding provides a new potential target for the treatment of HS.
