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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: (463 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 934 kb]
(146 Downloads)
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Type of Study: Original Research |
Subject:
Radiation Biology
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1. 1. Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, et al. (2022) The etiology of preeclampsia. Am J Obstet Gynecol, 226(2s): S844-s66. [ DOI:10.1016/j.ajog.2021.11.1356] 2. MacDonald TM, Walker SP, Hannan NJ, Tong S, Kaitu'u-Lino TJ (2022) Clinical tools and biomarkers to predict preeclampsia. EBioMedicine, 75: 103780. [ DOI:10.1016/j.ebiom.2021.103780] 3. Zhou W, Wang H, Yang Y, Guo F, Yu B, Su Z (2022) Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single-Cell RNA Sequencing. Mol Cells, 45(5): 317-28. [ DOI:10.14348/molcells.2021.0211] 4. Bakrania BA, George EM, Granger JP (2022) Animal models of preeclampsia: investigating pathophysiology and therapeutic targets. Am J Obstet Gynecol, 226(2s): S973-s87. [ DOI:10.1016/j.ajog.2020.10.025] 5. Peñailillo R, Acuña-Gallardo S, García F, Monteiro LJ, Nardocci G, Choolani MA, et al. (2022) Mesenchymal stem cells-induced trophoblast invasion is reduced in patients with a previous history of preeclampsia. Int J Mol Sci, 23(16): 9071. [ DOI:10.3390/ijms23169071] 6. Conese M, Napolitano O, Laselva O, Di Gioia S, Nappi L, Trabace L, et al. (2023) The Oncogenic Theory of Preeclampsia: Is Amniotic Mesenchymal Stem Cells-Derived PLAC1 Involved? Int J Mol Sci, 24(4): 3612. [ DOI:10.3390/ijms24043612] 7. Liu H and Tang T (2023) MAPK signaling pathway-based glioma subtypes, machine-learning risk model, and key hub proteins identification. Sci Rep, 13(1): 19055. [ DOI:10.1038/s41598-023-45774-0] 8. Liu H and Li Y (2022) Potential roles of Cornichon Family AMPA Receptor Auxiliary Protein 4 (CNIH4) in head and neck squamous cell carcinoma. Cancer Biomark, 35(4) :439-50. [ DOI:10.3233/CBM-220143] 9. Dhangar S, Shanmukhaiah C, Sawant L, Ghatanatti J, Shah A, Mathan SL, et al. (2023) Synergetic effect of Azacitidine and Sorafenib in treatment of a case of myeloid neoplasm with sole chromosomal abnormality t(8;22)(p11.2;q11.2)/BCR-FGFR1 rearrangement. Cancer Genet, 274-275: 26-9. [ DOI:10.1016/j.cancergen.2023.03.004] 10. Giri J and Modi D (2023) Endometrial and placental stem cells in successful and pathological pregnancies. J Assist Reprod Genet, 40(7): 1509-22. [ DOI:10.1007/s10815-023-02856-2] 11. Romberg SI, Kreis N-N, Friemel A, Roth S, Souto AS, Hoock SC, et al. (2022) Human placental mesenchymal stromal cells are ciliated and their ciliation is compromised in preeclampsia. BMC Medicine, 20(1): 35. [ DOI:10.1186/s12916-021-02203-1] 12. Zhaoer Y, Mingming G, Wei Z, Dan Y, Yating Q, Ruizhe J (2022) Extracellular vesicles for the treatment of preeclampsia. Tissue Cell, 77: 101860. [ DOI:10.1016/j.tice.2022.101860] 13. Zhao W, Li W, Zuo J, Zhou H, Gao G, Ye Y, et al. (2025) Exosomes secreted from amniotic mesenchymal stem cells modify trophoblast activities by delivering miR-18a-5p and regulating HRK-p53 interaction. Stem Cells, 43(3): sxae087. [ DOI:10.1093/stmcls/sxae087] 14. Shi J and Su M (2024) HMOX1 participates in pre-eclampsia by regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells via VEGF. Biochem Genet, 62(2): 1248-62. [ DOI:10.1007/s10528-023-10474-x] 15. Chen F, Cen H, Mao D, Feng R (2023) Placental homing peptide guides HIF1α-silenced exosomes conjugates for targeted enhancement of invasion of trophoblast cells. Mol Med Rep, 28(1): 135. [ DOI:10.3892/mmr.2023.13022] 16. Shao H, Guan R, Chen Z, Kong R, Zhang C, Gu H (2024) Circular RNA circ-0022707 impedes the progression of preeclampsia via the miR-3135b/GHR/PI3K/Akt axis. Functional & Integrative Genomics, 24(6): 208. [ DOI:10.1007/s10142-024-01490-0] 17. Wang R, Liu W, Zhao J, Liu L, Li S, Duan Y, et al. (2023) Overexpressed LAMC2 promotes trophoblast over-invasion through the PI3K/Akt/MMP2/9 pathway in placenta accreta spectrum. J Obstet Gynaecol Res, 49(2): 548-59. [ DOI:10.1111/jog.15493] |
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Liu H, Tan L. 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. Int J Radiat Res 2026; 24 (2) :495-500 URL: http://ijrr.com/article-1-7041-en.html
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