Protective effect of hUC-MSCs regulating peritoneal mesothelial cell EMT through cGAS-STING signaling pathway in high glucose-induced peritoneal fibrosis

doi:10.4252/wjsc.120270

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World Journal of Stem Cells

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1948-0210

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Stem Cells. Aug 26, 2026; 18(8): 120270
Published online Aug 26, 2026. doi: 10.4252/wjsc.120270

Protective effect of hUC-MSCs regulating peritoneal mesothelial cell EMT through cGAS-STING signaling pathway in high glucose-induced peritoneal fibrosis

Fu-Xing Dong, Lu-Li Zheng, Kun Nie, Jian-Xin Wan

Fu-Xing Dong, Jian-Xin Wan, Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China

Fu-Xing Dong, Department of Nephrology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, Fujian Province, China

Fu-Xing Dong, Jian-Xin Wan, Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China

Fu-Xing Dong, Jian-Xin Wan, Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China

Lu-Li Zheng, Kun Nie, Department of Blood Purification, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China

Author contributions: Wan JX conceived and designed the experiments; Dong FX carried out the experiments and drafted the manuscript; Zheng LL and Nie K carried out the experiments and revised the manuscript.

AI contribution statement: No generative artificial intelligence tools were used in any stage of this paper.

Supported by Natural Science Foundation of Fujian Province, No. 2021J01355.

Institutional animal care and use committee statement: All animal studies were conducted in accordance with the Animal Use Protocol and were approved by the Ethics Committee of Zvast-Bio Technology Co., Ltd. (No. 20240819).

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 datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Corresponding author: Jian-Xin Wan, Chief Physician, Professor, Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou 350005, Fujian Province, China. wanjx@fjmu.edu.cn

Received: February 24, 2026
Revised: April 2, 2026
Accepted: May 18, 2026
Published online: August 26, 2026
Processing time: 179 Days and 22.4 Hours

Abstract

BACKGROUND

Peritoneal dialysis represents one of the primary alternative therapies for end-stage renal disease. Peritoneal fibrosis (PF) may, however, develop as a consequence of the peritoneum being exposed to non-physiological peritoneal dialysis fluid over extended durations. PF is the main factor that forces end-stage renal disease patients to discontinue long-term peritoneal dialysis. Therefore, how to delay and block the progression of PF has surfaced as an issue demanding timely scholarly attention. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have a reversing effect on the fibrosis levels of various tissues. We hypothesized that hUC-MSCs may afford protection in PF.

AIM

To investigate the modulatory potential of hUC-MSCs across both in vivo and in vitro experimental models of PF.

METHODS

Both the in vivo and in vitro PF models displayed differential expression of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Next, hUC-MSC-mediated effects on epithelial-mesenchymal transition (EMT) driven by high glucose (HG) in HMrSV5 cells were determined. We also performed a rescue experiment with the STING agonist DMXAA to validate the engagement of the cGAS-STING signaling cascade in this event. The anti-fibrotic potential of hUC-MSCs was lastly investigated in a mouse model of PF.

RESULTS

Heightened levels of cGAS and STING proteins were discernible in both HG-exposed HMrSV5 cells and the mouse PF model. The presence of hUC-MSCs in co-culture exerted a potent suppressive influence on HG-evoked migratory, invasive, and EMT-related molecular changes in HMrSV5 cells. DMXAA-mediated intervention nullified the protective capacity of hUC-MSCs against HG-occasioned EMT in HMrSV5 cells. In addition, hUC-MSC intervention in PF mice dually mitigates peritoneal fibrotic alterations and inflammatory infiltration while lowering the protein expression of cGAS-STING pathway components.

CONCLUSION

The cGAS-STING pathway is activated in PF models both in vivo and in vitro, hUC-MSCs inhibit this pathway to suppress EMT in HMrSV5 cells and retard PF progression in mice.

Keywords: Human umbilical cord mesenchymal stem cells; Peritoneal fibrosis; Cyclic GMP-AMP synthase-stimulator of interferon genes signaling pathway; Epithelial-mesenchymal transition; Inflammation

Core Tip: The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is activated in peritoneal fibrosis (PF). This study shows that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) alleviate high glucose-induced epithelial-mesenchymal transition and murine PF. Mechanistically, hUC-MSCs exert protective effects by inhibiting the cGAS-STING axis. These findings identify hUC-MSCs as a promising therapeutic strategy to retard PF progression by targeting the cGAS-STING pathway in patients undergoing long-term peritoneal dialysis.