hucMSC-Ex Alleviates IBD-Associated Intestinal Fibrosis by Inhibiting ERK Phosphorylation in Intestinal Fibroblasts

Yifei Wang; Yaqin Zhang; Bing Lu; Jianbo Xi; Dickson Kofi Wiredu Ocansey; Fei Mao; Donglin Hao; Yongmin Yan

doi:10.1155/2023/2828981

hucMSC-Ex Alleviates IBD-Associated Intestinal Fibrosis by Inhibiting ERK Phosphorylation in Intestinal Fibroblasts

Stem Cells Int. 2023 Feb 17:2023:2828981. doi: 10.1155/2023/2828981. eCollection 2023.

Authors

Yifei Wang^{1

2}, Yaqin Zhang^{1

2}, Bing Lu³, Jianbo Xi^{1

4}, Dickson Kofi Wiredu Ocansey¹, Fei Mao¹, Donglin Hao¹, Yongmin Yan^{1

4

5}

Affiliations

¹ Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Jiangsu University, 213017 Changzhou, China.
² Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, 212013 Zhenjiang, China.
³ Zhenjiang College, 212028 Zhenjiang, China.
⁴ Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine, 213017 Changzhou, China.
⁵ Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University (Wujin Clinical College of Xuzhou Medical University), Jiangsu University, 213017 Changzhou, China.

Abstract

Background: Intestinal fibrosis, one of the complications of inflammatory bowel disease (IBD), is associated with fistula and intestinal stricture formation. There are currently no treatments for fibrosis. Mesenchymal stem cell-derived exosomes have been proven to exert inhibitory and reversal effects in IBD and other organ fibrosis. In this study, we explored the role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) in IBD-related fibrosis and its associated mechanism to provide new ideas for the prevention and treatment of IBD-related intestinal fibrosis.

Methods: We established a DSS-induced mouse IBD-related intestinal fibrosis model and observed the effect of hucMSC-Ex on the mouse model. We also used the TGF-induced human intestinal fibroblast CCD-18Co to observe the role of hucMSC-Ex in the proliferation, migration, and activation of intestinal fibroblasts. Having observed that the extracellular-signal-regulated kinase (ERK) pathway in intestinal fibrosis can be inhibited by hucMSC-Ex, we treated intestinal fibroblasts with an ERK inhibitor to emphasize the potential target of ERK phosphorylation in the treatment of IBD-associated intestinal fibrosis.

Results: In the animal model of IBD-related fibrosis, hucMSC-Ex alleviated inflammation-related fibrosis as evident in the thinning of the mice's intestinal wall and decreased expression of related molecules. Moreover, hucMSC-Ex inhibited TGF-β-induced proliferation, migration, and activation of human intestinal fibroblasts, and ERK phosphorylation played a key role in IBD-associated fibrosis. The inhibition of ERK decreased the expression of fibrosis-related indicators such as α-SMA, fibronectin, and collagen I.

Conclusion: hucMSC-Ex alleviates DSS-induced IBD-related intestinal fibrosis by inhibiting profibrotic molecules and intestinal fibroblast proliferation and migration by decreasing ERK phosphorylation.