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Adipose-derived stem cells promote the recovery of intestinal barrier function by inhibiting the p38 MAPK signaling pathway

Authors

Mei Yang
ym13987413637@163.com
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.
Wangbin Xu
Department of Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Chaofu Yue
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.
Rong Li
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.
Xian Huang
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.
Yongjun Yan
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.
Qinyong Yan
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.
Shisheng Liu
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.
Yuan Liu
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.
Qiaolin Li
Department of Critical Care Medicine, The Qujing No.1 People's Hospital, Qujing, China.

Intestinal barrier damage causes an imbalance in the intestinal flora and microbial environment, promoting a variety of gastrointestinal diseases. This study aimed to explore the mechanism by which adipose-derived stem cells (ADSCs) repair intestinal barrier damage. The human colon adenocarcinoma cell line Caco-2 and rats were treated with lipopolysaccharide (LPS) to establish in vitro and in vivo models, respectively, of intestinal barrier damage. The expression of inflammatory cytokines (TNF-α, HMGB1, IL-1β and IL-6), antioxidant enzymes (iNOS, SOD and CAT), and oxidative products (MDA and 8-iso-PGF2α) was detected using ELISA kits and related reagent kits. Apoptosis-related proteins (Bcl-2, Bax, Caspase-3 and Caspase-9), tight junction proteins (ZO-1, Occludin, E-cadherin, and Claudin-1) and p38 MAPK pathway-associated protein were detected by Western blotting. In addition, cell viability and apoptosis was determined by a CCK-8 kit and flow cytometry, respectively. Cell permeability was assayed by the transepithelial electrical resistance value and FITC-dextran concentration. The homing effect of ADSCs was detected by fluorescence labeling, and intestinal barrier tissue was observed by HE staining. After ADSC treatment, the level of phosphorylated p38 MAPK protein decreased, the expression of inflammatory factors, oxidative stress and cell apoptosis decreased, the expression of tight junction proteins increased, and cell permeability decreased in Caco-2 cells stimulated with LPS. In rats, ADSCs are directionally recruited to damaged intestinal tissue. ADSCs significantly decreased the levels of D-lactate, diamine oxidase (DAO) and FITC-dextran induced by LPS. ADSCs promoted tight junction proteins and inhibited oxidative stress in intestinal tissue. These effects were reversed after the use of a p38 MAPK activator. ADSCs can be directionally recruited to intestinal tissue, upregulate tight junction proteins, and reduce apoptosis and oxidative stress by inhibiting the p38MAPK signaling pathway. This study provides novel insights into the treatment of intestinal injury.

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Ethics Approval

this study was approved by the Animal Ethics Committee of Kunming Medical University Animal Center

Supporting Agencies

Yunnan Provincial Science and Technology Plan Project

How to Cite

Yang, M., Xu, W., Yue, C., Li, R., Huang, X., Yan, Y., … Li, Q. (2025). Adipose-derived stem cells promote the recovery of intestinal barrier function by inhibiting the p38 MAPK signaling pathway. European Journal of Histochemistry, 69(1). https://doi.org/10.4081/ejh.2025.4158
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