SIRT1-modified human umbilical cord mesenchymal stem cells ameliorate experimental peritoneal fibrosis by inhibiting the TGF-β/Smad3 pathway

被引:17
作者
Guo, Yanhong [2 ]
Wang, Liuwei [2 ]
Gou, Rong [2 ]
Wang, Yulin [2 ]
Shi, Xiujie [1 ]
Pang, Xinxin [1 ]
Tang, Lin [2 ]
机构
[1] Henan Univ Chinese Med, Hosp Affiliated 2, Henan Prov Hosp Tradit Chinese Med, Dept Nephropathy, 6 Dong Feng Rd, Zhengzhou 450002, Henan, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Nephropathy, 1 East Jianshe Rd, Zhengzhou 450052, Henan, Peoples R China
关键词
Peritoneal fibrosis; SIRT1; hUCMSCs; EMT; TGF-beta; PLATELET-RICH PLASMA; CARDIAC FIBROSIS; LIVER FIBROSIS; ACTIVATION; PROTECTS; HEALTH;
D O I
10.1186/s13287-020-01878-2
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Introduction: 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. Methods: SIRT1 was overexpressed in hUCMSCs to establish SIRT1-modified hUCMSCs. Co-culture and transplantation experiments were performed in TGF-beta-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. Results: 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-beta/Smad3 pathway in peritoneal omentum tissues. Conclusion: SIRT1-modified hUCMSCs might work as a promising therapeutic strategy for the treatment of peritoneal dialysis-induced peritoneal damage and fibrosis.
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页数:12
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