Exosomal miR­194 from adipose­derived stem cells impedes hypertrophic scar formation through targeting TGF­ß1.

ABSTRACT

Hypertrophic scars, which result from aberrant fibrosis and disorganized collagen synthesis by skin fibroblasts, emerge due to disrupted wound healing processes. These scars present significant psychosocial and functional challenges to affected individuals. The current treatment limitations largely arise from an incomplete understanding of the underlying mechanisms of hypertrophic scar development. Recent studies, however, have shed light on the potential of exosomal non­coding RNAs interventions to mitigate hypertrophic scar proliferation. The present study assessed the impact of exosomes derived from adipose­derived stem cells (ADSCs­Exos) on hypertrophic scar formation using a rabbit ear model. It employed hematoxylin and eosin staining, Masson's trichrome staining and immunohistochemical staining techniques to track scar progression. The comprehensive analysis of the present study encompassed the differential expression of non­coding RNAs, enrichment analyses of functional pathways, protein­protein interaction studies and micro (mi)RNA­mRNA interaction investigations. The results revealed a marked alteration in the expression levels of long non­coding RNAs and miRNAs following ADSCs­Exos treatment, with little changes observed in circular RNAs. Notably, miRNA (miR)­194 emerged as a critical regulator within the signaling pathways that govern hypertrophic scar formation. Dual­luciferase assays indicated a significant reduction in the promoter activity of TGF­ß1 following miR­194 overexpression. Reverse transcription­quantitative PCR and immunoblotting assays further validated the decrease in TGF­ß1 expression in the treated samples. In addition, the treatment resulted in diminished levels of inflammatory markers IL­1ß, TNF­α and IL­10. In vivo evidence strongly supported the role of miR­194 in attenuating hypertrophic scar formation through the suppression of TGF­ß1. The present study endorsed the strategic use of ADSCs­Exos, particularly through miR­194 modulation, as an effective strategy for reducing scar formation and lowering pro­inflammatory and fibrotic indicators such as TGF­ß1. Therefore, the present study advocated the targeted application of ADSCs­Exos, with an emphasis on miR­194 modulation, as a promising approach to managing proliferative scarring.