Scholarlink

<p>Sepsis-induced acute kidney injury (S-AKI) is a life-threatening condition driven by excessive immune inflammation, and effective treatments remain lacking. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have been demonstrated to possess potent immunomodulatory activity. This study aimed to investigate the role and underlying mechanism of MSC-sEV in S-AKI. We established in vivo and in vitro models of S-AKI and employed techniques such as small RNA sequencing, transcriptome sequencing, luciferase reporter assays, and engineered gene editing to validate therapeutic efficacy and elucidate mechanisms. Results demonstrated that in S-AKI, MSC-sEV homed to injured kidneys and were internalized by renal tubular epithelial cells, significantly ameliorating renal damage and improving survival rates. Mechanistically, MSC-sEV delivered miR-125a-5p to target and inhibit TNFR2 expression, thereby blocking TNF-driven pyroptosis mediated by the NF-κB/NLRP3 signaling pathway. Furthermore, engineered modification with the EXOMotif GGAG significantly enhanced MSC-sEV delivery of miR-125a-5p and inhibition of TNFR2. In conclusion, this study demonstrates that MSC-sEV represent a promising drug delivery vehicle with substantial targeted therapeutic potential for S-AKI.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mesenchymal stem cell-derived small extracellular vesicles suppress pyroptosis by delivering miR-125a-5p to improve acute kidney injury in sepsis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月19日

查看全文
  • Feng Chen,
  • Tao-Tao Tang,
  • Zhi-Qing Chen,
  • Qin Yang,
  • Yue Zhang,
  • Yi-Lin Zhang,
  • Jing Song,
  • Meng-Yun Wang,
  • Hong-Bin Yang,
  • Min Yang,
  • Suo-Fu Qin,
  • Zhe Guo,
  • Xue-Song Wang,
  • Zhong Wang,
  • Lin-Li Lv,
  • Bi-Cheng Liu

摘要

Sepsis-induced acute kidney injury (S-AKI) is a life-threatening condition driven by excessive immune inflammation, and effective treatments remain lacking. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have been demonstrated to possess potent immunomodulatory activity. This study aimed to investigate the role and underlying mechanism of MSC-sEV in S-AKI. We established in vivo and in vitro models of S-AKI and employed techniques such as small RNA sequencing, transcriptome sequencing, luciferase reporter assays, and engineered gene editing to validate therapeutic efficacy and elucidate mechanisms. Results demonstrated that in S-AKI, MSC-sEV homed to injured kidneys and were internalized by renal tubular epithelial cells, significantly ameliorating renal damage and improving survival rates. Mechanistically, MSC-sEV delivered miR-125a-5p to target and inhibit TNFR2 expression, thereby blocking TNF-driven pyroptosis mediated by the NF-κB/NLRP3 signaling pathway. Furthermore, engineered modification with the EXOMotif GGAG significantly enhanced MSC-sEV delivery of miR-125a-5p and inhibition of TNFR2. In conclusion, this study demonstrates that MSC-sEV represent a promising drug delivery vehicle with substantial targeted therapeutic potential for S-AKI.