Abstract
Inflammatory bowel diseases (IBDs) are prevalent and debilitating diseases with limited clinical treatment strategies. Mesenchymal stem cell (MSCs) are pluripotent stem cells with self-renewal capability and multiple immunomodulatory effects, which make them a promising therapeutic approach for IBDs. Thus, optimization of MSCs regimes is crucial for their further clinical application. Wogonin, a flavonoid-like compound with extensive immunomodulatory and adjuvant effects, has been investigated as a potential pretreatment for MSCs in IBD treatment. In this study, we employed the DSS-induced acute colitis mouse model to compare the therapeutic effectiveness of MSCs in pretreated with or without wogonin and further explore the underlying mechanism. Compared to untreated MSCs, MSCwogonin (pretreated with wogonin) showed greater effectiveness in the treatment of colitis. Further experiments revealed that wogonin treatment activated the AKT signaling pathway, resulting in higher cellular glycolysis. Inhibition of AKT phosphorylation by perifosine not only decreased glycolysis but impaired the therapeutic efficiency of MSCwogonin. Consistent with these results, qPCR data indicated that wogonin treatment induced the expression of immunomodulatory molecules IL-10, IDO, and AGR1, which were reduced by perifosine. Together, our data demonstrated that wogonin preconditioning strategy further augmented the therapeutic efficacy of MSCs via promoting glycolysis, which should be a promising strategy for optimizing MSCs therapy in IBDs.
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The datasets generated or analyzed for the present study are available from the corresponding author upon reasonable request.
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Funding
This work is supported by the National Natural Science Foundation of China (NO. 82170216), Fundamental and Applied Basic Research of Guangzhou City-University (Institution) Projects (NO. 202201020461), Science and Technology Program of Guangzhou (NO. 202102020738, NO. 202102080468), Sanming Project of Medicine in Shenzhen Nanshan (NO. SZSM202103012), Shenzhen Nanshan District Science and Technology Program (NO. NS2022023).
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All authors contributed to the study conception and design. Mengye Wu, Cuiping Li and Xue Zhou performed the research and interpreted the data. Ming, Pan, Zhiyong Wu and Xiaorong Lai established a mouse model of IBD. Qinghai Lian performed metabolic analysis. Jianqi Feng, Xiaolu Guo and Rui Fang performed RNA-seq analysis, qPCR and western blotting. Yanwen Peng and Mengye Wu wrote the manuscript and all authors commented on previous versions of the manuscript. Yanwen Peng supervised the project. All authors have read and approved the final manuscript.
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All of the experimental animal protocols were approved by the Sun Yat-sen University Institutional Animal Care and Use Committee. (reference number: SYSU-IACUC-2020-000423, approval date: 2020.11.23).
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Wu, M., Li, C., Zhou, X. et al. Wogonin preconditioning of MSCs improved their therapeutic efficiency for colitis through promoting glycolysis. Inflammopharmacol (2024). https://doi.org/10.1007/s10787-024-01491-2
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DOI: https://doi.org/10.1007/s10787-024-01491-2