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Mechanism of mesenchymal stem cell-derived exosomes in regulating the proliferation, migration, and invasion of trophoblasts in preeclampsia via the PI3K/AKT pathway: Insights relevant to tumor biology and radiotherapy resistance
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H. Liu   , L. Tan |
| Department of Obstetrical, Beidahuang Industry Group General Hospital, Harbin 150000, Heilongjiang Province, China , liuhuimin1221@163.com |
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Abstract: (13 Views) |
Background: Radiotherapy, while primarily used in oncology, can induce significant cellular stress in non-target tissues, including hypoxia-like conditions, oxidative damage, and impaired cell function. Trophoblast cell lines exposed to X-ray irradiation exhibit suppressed proliferation, migration, and invasion-phenomena that closely mimic trophoblast dysfunction under placental stress and radioresistance mechanisms in tumor cells. This study aimed to investigate the protective mechanism of Mesenchymal stem cell-derived exosomes (MSCs-Exos) on X-ray irradiated HTR-8/SVneo trophoblast cells, focusing on restoration of proliferation, migration, and invasion capacities through activation of the PI3K/AKT signaling pathway. Materials and Methods: HTR-8/SVneo cells were subjected to 6 Gy X-ray irradiation to establish a radiation-injury model. Experimental groups included: normal control (CG), irradiation model (MG), exosome intervention (EG; 100 μg/mL MSCs-Exos post-irradiation), and PI3K inhibitor (IG; LY294002 + MSCs-Exos). Cell proliferation (CCK-8), migration and invasion (Transwell), PI3K/AKT pathway activation (Western blot), inflammatory cytokines (ELISA), and oxidative stress markers (ROS, MDA, SOD) were evaluated. Results: X-ray irradiation significantly impaired proliferation, migration, and invasion while downregulating p-PI3K and p-AKT expression and increasing inflammatory cytokines and oxidative stress (all P < 0.001). MSCs-Exos treatment markedly reversed these effects, restoring functional capacities, reactivating PI3K/AKT, and alleviating inflammation and oxidative damage. These benefits were attenuated by LY294002. Conclusion: MSCs-Exos protect X-ray-irradiated trophoblast cells against radiation-induced injury by activating the PI3K/AKT pathway. The findings highlight a novel radioprotective role of MSCs-Exos and provide mechanistic insights applicable to radiation-induced placental injury models and tumor radioresistance. |
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| Keywords: Exosomes, mesenchymal stem cells, trophoblasts, ionizing radiation, PI3K/AKT pathway, radiation protection. |
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Full-Text [PDF 936 kb]
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Type of Study: Original Research |
Subject:
Radiation Biology
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