Extracellular vesicles produced by bone marrow mesenchymal stem cells overexpressing programmed death‐ligand 1 ameliorate dextran sodium sulfate‐induced ulcerative colitis in rats by regulating Th17/Treg cell balance through PTEN/PI3K/AKT/mTOR axis
| العنوان: | Extracellular vesicles produced by bone marrow mesenchymal stem cells overexpressing programmed death‐ligand 1 ameliorate dextran sodium sulfate‐induced ulcerative colitis in rats by regulating Th17/Treg cell balance through PTEN/PI3K/AKT/mTOR axis |
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| المؤلفون: | Hongxia He, Qianyun Chen, Heng Fan, Xue yuan Leng, Feng Zhu, Fei Gao, Qiaoli Zhou, Yalan Dong, Jia Yang |
| المصدر: | Journal of Gastroenterology and Hepatology. 37:2243-2254 |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Phosphatidylinositol 3-Kinases, Extracellular Vesicles, Hepatology, TOR Serine-Threonine Kinases, PTEN Phosphohydrolase, Gastroenterology, Animals, Th17 Cells, Dextrans, Mesenchymal Stem Cells, T-Lymphocytes, Regulatory, B7-H1 Antigen, Rats |
| الوصف: | Programmed death-ligand 1 (PD-L1) was involved in regulating Th17/Treg cell balance in ulcerative colitis (UC). Extracellular vesicles (EVs) from genetically modified bone marrow mesenchymal stem cells (BMSCs) can serve as a stable delivery system to overexpress PD-L1. The study was designed to evaluate the therapeutic mechanism of BMSC-EVs overexpressing PD-L1 (PD-L1-EVs) on ulcerative colitis.Experimental model of UC was established in rats by drinking 5% dextran sulfate sodium (DSS). Apoptosis-related proteins, inflammatory response-related factors and oxidative stress related mediators were detected. Westernblot was used to detecte key proteins in the PI3K/AKT signaling pathway and its downstream effectors. The CD4PD-L1-EVs significantly alleviated the manifestations and pathological damage of UC rats by inhibiting the expression of IFN-γ, IL-1β, IL-8, IL-6, IL-2, BAX, NF-κB, TNF-α, MPO, and MDA, and up-regulating the expression of IL-4, BCL-2, SOD, and GSH. Furthermore, the proportions of Th17 cells were decreased and that of Treg cells were upregulated by PD-L1-EVs treatment. PTEN inhibitors (bpv) partially abolished the inhibitory effect of PD-L1-EVs on PI3K-AKT signaling and impaired the therapeutic efficacy of PD-L1-EVs.PD-L1-EVs mitigated colonal inflammation, apoptosis and oxidative stress through blocking the activation of PI3K/Akt/mTOR pathway and regulating the balance of Th17/Treg cells. |
| تدمد: | 1440-1746 0815-9319 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::81a126f6308d1a56a59b7116106e5128 https://doi.org/10.1111/jgh.15987 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....81a126f6308d1a56a59b7116106e5128 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14401746 08159319 |
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