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World J Stem Cells. Jun 26, 2026; 18(6): 120457
Published online Jun 26, 2026. doi: 10.4252/wjsc.120457
Published online Jun 26, 2026. doi: 10.4252/wjsc.120457
ENaCδ aggravates gastroesophageal reflux disease via PI3K/AKT/mTOR: Human umbilical cord mesenchymal stem cells restore barrier function
Cong Wang, Jun Wan, Department of Gastroenterology, The Second Medical Center of Chinese PLA General Hospital, Beijing 100853, China
Yi Li, Qian-Qian Chen, Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
Co-corresponding authors: Qian-Qian Chen and Jun Wan.
Author contributions: Wang C and Wan J designed the study, performed the experiments and prepared the manuscript; Li Y collected the data; Wang C and Chen QQ analyzed the data; and all authors read and approved the final manuscript.
Supported by Beijing Natural Science Foundation, No. 7232151.
Institutional animal care and use committee statement: All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of the First Medical Center of Chinese PLA General Hospital (No. SR20250327), and were conducted in accordance with relevant guidelines and regulations.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Jun Wan, MD, Department of Gastroenterology, The Second Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. wanjun_301@126.com
Received: March 3, 2026
Revised: March 31, 2026
Accepted: May 7, 2026
Published online: June 26, 2026
Processing time: 114 Days and 0.7 Hours
Revised: March 31, 2026
Accepted: May 7, 2026
Published online: June 26, 2026
Processing time: 114 Days and 0.7 Hours
Core Tip
Core Tip: We developed a CRISPR/Cas9-generated humanized epithelial sodium channel δ mouse model to better mimic human gastroesophageal reflux disease. Humanized epithelial sodium channel δ aggravated acid-induced esophageal inflammation by activating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, increasing interleukin 1 (IL-1), IL-1β, IL-17 and inducible nitric oxide synthase, and impairing barrier and contractile regulators (claudin-1 and myosin phosphatase target subunit 1). Human umbilical cord mesenchymal stem cells reversed these changes and outperformed proton pump inhibitor in suppressing IL-17 and restoring claudin-1/myosin phosphatase target subunit 1.