miR-21-loaded bone marrow mesenchymal stem cell-derived exosomes inhibit pyroptosis by targeting MALT1 to repair chemotherapy-induced premature ovarian insufficiency.

Autor: Tang L; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Yang Y; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Yang M; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Xie J; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Zhuo A; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Wu Y; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Mao M; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Zheng Y; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China., Fu X; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. fxf1997@smu.edu.cn.
Jazyk: angličtina
Zdroj: Cell biology and toxicology [Cell Biol Toxicol] 2024 Dec 20; Vol. 41 (1), pp. 3. Date of Electronic Publication: 2024 Dec 20.
DOI: 10.1007/s10565-024-09946-6
Abstrakt: Chemotherapy is essential for treating malignant tumors, but it can cause premature ovarian insufficiency (POI). Recent studies suggest that exosomes enriched with miR-21 (miR-21-Exo) may help mitigate POI, though the underlying mechanisms remain largely unexplored. This research investigates how miR-21-Exo influences chemotherapy-induced POI using an experimental model where KGN cells are exposed to cisplatin. We assessed the impact of miR-21 on cellular activity and generated miR-21 overexpressing bone marrow mesenchymal stem cells (miR-21-BMSC) via lentiviral modification. Isolated miR-21-Exo was analyzed for its effects on cellular function. Bioinformatics identified Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT1) as a target of miR-21. We confirmed that miR-21-Exo regulates MALT1 and the NF-κB signaling pathway to prevent cell pyroptosis. Further studies in a rat model demonstrated the therapeutic potential and safety of miR-21-Exo. Overall, our findings highlight a novel strategy for addressing chemotherapy-induced POI by modulating MALT1 and the NF-κB pathway, offering significant therapeutic implications.
Competing Interests: Declarations. Ethics approval and informed consent: All animal experiments conducted was compliant with the Ethics Committee of Southern Medical University Zhujiang Hospital (Nọ: LAEC-2022–208). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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