PMID- 37229651 OWN - NLM STAT- MEDLINE DCOM- 20230607 LR - 20230627 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 15 IP - 10 DP - 2023 May 23 TI - Mechanisms of human umbilical cord mesenchymal stem cells-derived exosomal lncRNA GAS5 in alleviating EMT of HPMCs via Wnt/beta-catenin signaling pathway. PG - 4144-4158 LID - 10.18632/aging.204719 [doi] AB - BACKGROUND: Prolonged peritoneal dialysis (PD) can result in epithelial-to-mesenchymal transition (EMT) and peritoneal fibrosis (PF), which can cause patients to discontinue PD. It is imperative to urgently investigate effective measures to mitigate PF. This study aims to reveal mechanisms of exosomal lncRNA GAS5 derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) on EMT of human peritoneal mesothelial cells (HPMCs) under high glucose (HG) conditions. METHODS: HPMCs were stimulated with 2.5% glucose. The effects on EMT of HPMCs were observed by using an hUC-MSC conditioned medium (hUC-MSC-CM) and extracted exosomes. After hUC-MSCs were transfected with GAS5 siRNA, exosomes were extracted to act on HPMCs for detecting EMT markers, PTEN, and Wnt/beta-catenin pathway, lncRNA GAS5 and miR-21 expressions in HPMCs. RESULTS: We found that HG could induce the EMT of HPMCs. Compared with the HG group, the hUC-MSC-CM could alleviate the EMT of HPMCs induced by HG through exosomes. Exosomes in the hUC-MSC-CM entered HPMCs, by transferring lncRNA GAS5 to HPMCs, which down-regulates miR-21 and up-regulates PTEN, thus finally alleviating EMT of HPMCs. The Wnt/beta-catenin pathway plays an essential role in alleviating EMT of HPMCs by exosomes in the hUC-MSC-CM. By transferring lncRNA GAS5 to HPMCs, exosomes derived from hUC-MSCs may competitively bind to miR-21 to regulate suppression on target PTEN genes and alleviate EMT of HPMCs through the Wnt/beta-catenin pathway. CONCLUSIONS: Exosomes from the hUC-MSCs-CM could alleviate the EMT of HPMCs induced by HG via regulating lncRNA GAS5/miR-21/PTEN through the Wnt/beta-catenin signaling pathway. FAU - Huang, Yuling AU - Huang Y AD - Department of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China. FAU - Ma, Jianfei AU - Ma J AD - Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China. FAU - Fan, Yi AU - Fan Y AD - Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China. FAU - Yang, Lina AU - Yang L AD - Department of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230523 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (RNA, Long Noncoding) RN - 0 (beta Catenin) RN - 0 (MicroRNAs) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Humans MH - Wnt Signaling Pathway MH - *RNA, Long Noncoding/genetics/metabolism MH - beta Catenin/metabolism MH - *MicroRNAs/genetics/metabolism MH - Glucose/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - Umbilical Cord/metabolism PMC - PMC10258012 OTO - NOTNLM OT - epithelial-mesenchymal transition OT - exosome OT - human peritoneal mesothelial cell OT - human umbilical cord mesenchymal stem cell OT - peritoneal dialysis COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to this study. EDAT- 2023/05/25 19:12 MHDA- 2023/06/07 06:42 PMCR- 2023/05/31 CRDT- 2023/05/25 16:43 PHST- 2023/01/08 00:00 [received] PHST- 2023/05/01 00:00 [accepted] PHST- 2023/06/07 06:42 [medline] PHST- 2023/05/25 19:12 [pubmed] PHST- 2023/05/25 16:43 [entrez] PHST- 2023/05/31 00:00 [pmc-release] AID - 204719 [pii] AID - 10.18632/aging.204719 [doi] PST - ppublish SO - Aging (Albany NY). 2023 May 23;15(10):4144-4158. doi: 10.18632/aging.204719. Epub 2023 May 23.