Kang Lin, Li Zhujun, Li Fangyuan, Li Ziming, Wang Liquan, Li Tianhao, Xiang Jieyu, Tseng Songlu, Yu Nanze, Huang Jiuzuo, Long Xiao
Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Stem Cells Int. 2025 May 9;2025:1416567. doi: 10.1155/sci/1416567. eCollection 2025.
Adipose-derived stem cells (ADSCs) demonstrated therapeutic potential in various fibrotic diseases, with their paracrine proteins playing a crucial role. Nonetheless, the principal paracrine factors of ADSCs responsible for antifibrosis have not yet been well identified. To address this issue, we initially confirmed that ADSCs could attenuate fibrosis and suppress TGF-1 in bleomycin-induced skin fibrosis mouse models. RNA-sequencing of the cocultured fibroblasts demonstrated that ADSCs effectively inhibited the TGF-/Smad2 signaling pathway in fibroblasts through the paracrine approach. Proteomic analysis of the cell supernatant (CS) demonstrated a significant upregulation of 97 proteins in the secretome of ADSCs, among which decorin (DCN) exhibited a particularly elevated level of overexpression. Protein-protein interaction (PPI) network analysis indicated a strong correlation between DCN and TGF-1, with DCN effectively trapping TGF-1 through core protein binding. Cell experiments demonstrated that DCN could effectively inhibit TGF-1-induced fibroblast proliferation. Therefore, it was concluded that DCN was a crucial protein in ADSC secretome that exerted antifibrotic effects by inhibiting TGF-1. This study conducted an in-depth insight into the paracrine function of ADSCs through transcriptome and proteome analysis, identifying DCN as an essential paracrine factor mediating the antifibrotic effect of ADSCs, which could provide valuable theoretical support for the use of ADSC secretions as well as DCN in the treatment of fibrotic diseases.
脂肪来源干细胞（ADSCs）在多种纤维化疾病中显示出治疗潜力，其旁分泌蛋白发挥着关键作用。尽管如此，ADSCs负责抗纤维化的主要旁分泌因子尚未得到很好的鉴定。为了解决这个问题，我们首先在博来霉素诱导的皮肤纤维化小鼠模型中证实，ADSCs可以减轻纤维化并抑制转化生长因子-1（TGF-1）。共培养成纤维细胞的RNA测序表明，ADSCs通过旁分泌途径有效抑制成纤维细胞中的TGF-β/Smad2信号通路。细胞上清液（CS）的蛋白质组分析表明，ADSCs分泌组中有97种蛋白质显著上调，其中核心蛋白聚糖（DCN）的过表达水平尤其升高。蛋白质-蛋白质相互作用（PPI）网络分析表明，DCN与TGF-1之间存在强相关性，DCN通过核心蛋白结合有效地捕获TGF-1。细胞实验表明，DCN可以有效抑制TGF-1诱导的成纤维细胞增殖。因此，得出结论，DCN是ADSC分泌组中的一种关键蛋白质，通过抑制TGF-1发挥抗纤维化作用。本研究通过转录组和蛋白质组分析对ADSCs的旁分泌功能进行了深入研究，确定DCN是介导ADSCs抗纤维化作用的重要旁分泌因子，可为ADSC分泌物以及DCN用于治疗纤维化疾病提供有价值的理论支持。
