Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD). Combination therapies are emerging as a promising treatment for tissue damage. Here, we investigated the therapeutic potential of SIRT1-modified human umbilical cord mesenchymal stem cells (hUCMSCs) for peritoneal fibrosis. SIRT1 was overexpressed in hUCMSCs to establish SIRT1-modified hUCMSCs. Co-culture and transplantation experiments were performed in TGF-β-stimulated Met-5A cells and peritoneal damage rodent model to assess the therapeutic potential of SIRT1-modified hUCMSCs for peritoneal fibrosis through qPCR, Western blot, and peritoneal function analyses. SIRT1-modified hUCMSC administration had more potent anti-fibrosis ability than hUCMSCs, which significantly inhibited the expression of fibrotic genes and suppressed EMT process, increased ultrafiltration volume, and restored homeostasis of bioincompatible factors in dialysis solution. Mechanistically, SIRT1-modified hUCMSCs attenuated peritoneal fibrosis through reducing peritoneal inflammation and inhibiting the TGF-β/Smad3 pathway in peritoneal omentum tissues. SIRT1-modified hUCMSCs might work as a promising therapeutic strategy for the treatment of peritoneal dialysis-induced peritoneal damage and fibrosis.

中文翻译：

---

SIRT1修饰的人脐带间充质干细胞通过抑制TGF-β/ Smad3途径改善了实验性腹膜纤维化。

腹膜纤维化是长期腹膜透析（PD）的严重并发症。组合疗法作为组织损伤的有前途的治疗方法正在兴起。在这里，我们调查了SIRT1修饰的人脐带间充质干细胞（hUCMSCs）对腹膜纤维化的治疗潜力。SIRT1在hUCMSC中过表达，以建立SIRT1修饰的hUCMSC。在TGF-β刺激的Met-5A细胞和腹膜损伤啮齿动物模型中进行共培养和移植实验，以通过qPCR，Western印迹和腹膜功能分析评估SIRT1修饰的hUCMSC对腹膜纤维化的治疗潜力。SIRT1修饰的hUCMSC给药比hUCMSC具有更强的抗纤维化能力，从而显着抑制纤维化基因的表达并抑制EMT过程，增加了超滤量，并恢复了透析液中生物不相容因子的体内平衡。从机制上讲，SIRT1修饰的hUCMSC通过减少腹膜发炎并抑制腹膜网膜组织中的TGF-β/ Smad3途径来减轻腹膜纤维化。SIRT1修饰的hUCMSCs可能是治疗腹膜透析引起的腹膜损伤和纤维化的有前途的治疗策略。