Wang Yifei, Zhang Yaqin, Lu Bing, Xi Jianbo, Ocansey Dickson Kofi Wiredu, Mao Fei, Hao Donglin, Yan Yongmin
Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Jiangsu University, 213017 Changzhou, China.
Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, 212013 Zhenjiang, China.
Stem Cells Int. 2023 Feb 17;2023:2828981. doi: 10.1155/2023/2828981. eCollection 2023.
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.
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.
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--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 -SMA, fibronectin, and collagen I.
hucMSC-Ex alleviates DSS-induced IBD-related intestinal fibrosis by inhibiting profibrotic molecules and intestinal fibroblast proliferation and migration by decreasing ERK phosphorylation.
肠道纤维化是炎症性肠病（IBD）的并发症之一，与瘘管和肠道狭窄形成有关。目前尚无针对纤维化的治疗方法。间充质干细胞衍生的外泌体已被证明在IBD和其他器官纤维化中发挥抑制和逆转作用。在本研究中，我们探讨了人脐带间充质干细胞衍生的外泌体（hucMSC-Ex）在IBD相关纤维化中的作用及其相关机制，为IBD相关肠道纤维化的预防和治疗提供新思路。
我们建立了DSS诱导的小鼠IBD相关肠道纤维化模型，并观察hucMSC-Ex对小鼠模型的影响。我们还使用TGF诱导的人肠道成纤维细胞CCD-18Co来观察hucMSC-Ex在肠道成纤维细胞增殖、迁移和激活中的作用。观察到hucMSC-Ex可抑制肠道纤维化中的细胞外信号调节激酶（ERK）通路后，我们用ERK抑制剂处理肠道成纤维细胞，以强调ERK磷酸化在治疗IBD相关肠道纤维化中的潜在靶点。
在IBD相关纤维化的动物模型中，hucMSC-Ex减轻了炎症相关纤维化，表现为小鼠肠壁变薄和相关分子表达降低。此外，hucMSC-Ex抑制了TGF诱导的人肠道成纤维细胞的增殖、迁移和激活，并且ERK磷酸化在IBD相关纤维化中起关键作用。抑制ERK可降低纤维化相关指标如α-SMA、纤连蛋白和I型胶原的表达。
hucMSC-Ex通过抑制促纤维化分子以及通过降低ERK磷酸化来抑制肠道成纤维细胞增殖和迁移，从而减轻DSS诱导的IBD相关肠道纤维化。
