The Plastic and Cosmetic Center, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China.
Mol Med Rep. 2024 Dec;30(6). doi: 10.3892/mmr.2024.13340. Epub 2024 Sep 27.
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 non‑coding RNAs interventions to mitigate hypertrophic scar proliferation. The present study assessed the impact of exosomes derived from adipose‑derived stem cells (ADSCs‑Exos) 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 non‑coding RNAs, enrichment analyses of functional pathways, protein‑protein interaction studies and micro (mi)RNA‑mRNA interaction investigations. The results revealed a marked alteration in the expression levels of long non‑coding RNAs and miRNAs following ADSCs‑Exos 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. Dual‑luciferase assays indicated a significant reduction in the promoter activity of TGF‑β1 following miR‑194 overexpression. Reverse transcription‑quantitative PCR and immunoblotting assays further validated the decrease in TGF‑β1 expression in the treated samples. In addition, the treatment resulted in diminished levels of inflammatory markers IL‑1β, TNF‑α and IL‑10. evidence strongly supported the role of miR‑194 in attenuating hypertrophic scar formation through the suppression of TGF‑β1. The present study endorsed the strategic use of ADSCs‑Exos, particularly through miR‑194 modulation, as an effective strategy for reducing scar formation and lowering pro‑inflammatory and fibrotic indicators such as TGF‑β1. Therefore, the present study advocated the targeted application of ADSCs‑Exos, with an emphasis on miR‑194 modulation, as a promising approach to managing proliferative scarring.
增生性瘢痕是由于皮肤成纤维细胞异常纤维化和胶原合成紊乱导致的，是由于伤口愈合过程被破坏而出现的。这些瘢痕会给患者带来显著的心理社会和功能挑战。目前的治疗局限性主要源于对增生性瘢痕发展潜在机制的不完全理解。然而，最近的研究揭示了外泌体非编码 RNA 干预减轻增生性瘢痕增殖的潜力。本研究使用兔耳模型评估了脂肪来源干细胞衍生的外泌体（ADSCs-Exos）对增生性瘢痕形成的影响。它采用苏木精和伊红染色、马松三色染色和免疫组织化学染色技术来跟踪瘢痕进展。本研究的综合分析包括非编码 RNA 的差异表达、功能途径的富集分析、蛋白质-蛋白质相互作用研究和 micro（mi）RNA-mRNA 相互作用研究。结果显示，ADSCs-Exos 处理后长非编码 RNA 和 miRNA 的表达水平发生明显改变，而环状 RNA 变化较小。值得注意的是，miRNA（miR）-194 是调控增生性瘢痕形成信号通路的关键调节因子。双荧光素酶报告基因实验表明，miR-194 过表达后 TGF-β1 启动子活性显著降低。逆转录定量 PCR 和免疫印迹实验进一步验证了处理样本中 TGF-β1 表达的降低。此外，该治疗还导致炎症标志物 IL-1β、TNF-α 和 IL-10 的水平降低。这些发现为 miR-194 通过抑制 TGF-β1 来减轻增生性瘢痕形成提供了有力证据。本研究支持通过 miR-194 调节策略来使用 ADSCs-Exos，作为减少瘢痕形成和降低 TGF-β1 等促炎和纤维化指标的有效策略。因此，本研究提倡靶向应用 ADSCs-Exos，重点调节 miR-194，作为治疗增生性瘢痕的一种有前途的方法。
