Research Paper Volume 15, Issue 14 pp 6921—6932
Exosomal lnc-CDHR derived from human umbilical cord mesenchymal stem cells attenuates peritoneal epithelial-mesenchymal transition through AKT/FOXO pathway
- 1 Department of Gastroenterology and Endoscopy, The First Hospital of China Medical University, Shenyang 110001, Liaoning, P.R. China
- 2 Department of Geriatrics, The First Hospital of China Medical University, Shenyang 110001, Liaoning, P.R. China
- 3 Department of Endodontics, School of Stomatology, China Medical University, Shenyang 110001, Liaoning, P.R. China
- 4 Department of International Physical Examination Center, The First Hospital of China Medical University, Shenyang 110001, Liaoning, P.R. China
Received: April 6, 2023 Accepted: June 23, 2023 Published: July 18, 2023
https://doi.org/10.18632/aging.204883How to Cite
Copyright: © 2023 Jiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Chronic stimulation of peritoneal dialysis (PD) fluid leads to the epithelial-mesenchymal transformation (EMT) of mesothelial cells, peritoneal fibrosis (PF), and ultimately ultrafiltration failure. Some studies have proposed that mesenchymal stem cells (MSCs) can alleviate PF. This study aimed to investigate whether the exosomes from human umbilical cord MSCs (hUMSCs) could alleviate peritoneal EMT.
Methods: Human peritoneal mesothelial cell line (HMrSV5) were treated with high glucose (HG) for 48 hours to induce the peritoneal EMT model. An inverted fluorescence microscope was used to observe the internalization of exosomes derived from hUMSCs (hUMSC-Exos). Western blot and real-time PCR were used to evaluate the expression of α-SMA, Vimentin, E-cadherin, PTEN, and AKT/FOXO3a. The relationships of lncRNA CDHR and miR-3149, miR-3149 and PTEN were detected by dual luciferase reporter gene assay.
Results: Compared with HG-induced HMrSV5, E-cadherin and PTEN levels significantly increased whereas α-SMA and Vimentin levels significantly decreased after treatment of hUMSC-CM and hUMSC-Exos (P < 0.05). An inverted fluorescence microscope showed HMrSV5 can absorb exosomes to alleviate EMT. Furthermore, exosomes extracted from lnc-CDHR siRNA-transfected hUMSCs can’t ameliorate HMrSV5 EMT. Moreover, both CDHR overexpressed and miR-3149 inhibitor in HG-induced HMrSV5 alleviated the expression of α-SMA, and Vimentin, and increased the expression of E-cadherin and PTEN, and AKT/FOXO3a. A rescue experiment showed that CDHR overexpressed expression was repressed by miR-3149 in the HG-induced peritoneal EMT model.
Conclusions: Exosomal lnc-CDHR derived from hUMSCs may competitively bind to miR-3149 to regulate suppression on target PTEN genes and alleviate EMT of HMrSV5 through AKT/FOXO pathway.
Abbreviations
PD: peritoneal dialysis; EMT: epithelial-mesenchymal transformation; PF: peritoneal fibrosis; MSCs: mesenchymal stem cells; hUMSCs: human umbilical cord MSCs; HG: high glucose; hUMSC-Exos: exosomes derived from hUMSCs; hUMSC-CM: culture medium from hUMSCs; cDNA: complementary DNA.