PMID- 32811535 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 11 IP - 1 DP - 2020 Aug 18 TI - SIRT1-modified human umbilical cord mesenchymal stem cells ameliorate experimental peritoneal fibrosis by inhibiting the TGF-beta/Smad3 pathway. PG - 362 LID - 10.1186/s13287-020-01878-2 [doi] LID - 362 AB - 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. FAU - Guo, Yanhong AU - Guo Y AD - Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China. FAU - Wang, Liuwei AU - Wang L AD - Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China. FAU - Gou, Rong AU - Gou R AD - Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China. FAU - Wang, Yulin AU - Wang Y AD - Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China. FAU - Shi, Xiujie AU - Shi X AD - Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Hospital Affiliated to Henan University of Chinese Medicine), No. 6, Dong Feng Road, Jinshui District, Zhengzhou, 450002, Henan, China. FAU - Pang, Xinxin AU - Pang X AD - Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Hospital Affiliated to Henan University of Chinese Medicine), No. 6, Dong Feng Road, Jinshui District, Zhengzhou, 450002, Henan, China. doctorpang@aliyun.com. FAU - Tang, Lin AU - Tang L AD - Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China. tanglin@zzu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200818 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (SMAD3 protein, human) RN - 0 (Smad3 Protein) RN - 0 (Transforming Growth Factor beta) RN - EC 3.5.1.- (SIRT1 protein, human) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Humans MH - *Mesenchymal Stem Cells/metabolism MH - *Peritoneal Fibrosis/genetics/therapy MH - Sirtuin 1/genetics MH - Smad3 Protein/genetics MH - Transforming Growth Factor beta/genetics/metabolism MH - Umbilical Cord/metabolism PMC - PMC7436980 OTO - NOTNLM OT - EMT OT - Peritoneal fibrosis OT - SIRT1 OT - TGF-beta OT - hUCMSCs COIS- The authors declare that there is no conflict of interests. EDAT- 2020/08/20 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/08/18 CRDT- 2020/08/20 06:00 PHST- 2020/04/29 00:00 [received] PHST- 2020/08/05 00:00 [accepted] PHST- 2020/07/01 00:00 [revised] PHST- 2020/08/20 06:00 [entrez] PHST- 2020/08/20 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/08/18 00:00 [pmc-release] AID - 10.1186/s13287-020-01878-2 [pii] AID - 1878 [pii] AID - 10.1186/s13287-020-01878-2 [doi] PST - epublish SO - Stem Cell Res Ther. 2020 Aug 18;11(1):362. doi: 10.1186/s13287-020-01878-2.