Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POI
Human amniotic mesenchymal stem cells (hAMSCs) were previously shown to effectively rescue ovarian function in a premature ovarian insufficiency (POI) mouse model. The therapeutic mechanism of hAMSC-derived exosomes (hAMSC-Exos) is not fully understood. In this study, the therapeutic mechanism invol...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120301396 |
| _version_ | 1818135409782161408 |
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| author | Chenyue Ding Chunfeng Qian Shunyu Hou Jiafeng Lu Qinyan Zou Hong Li Boxian Huang |
| author_facet | Chenyue Ding Chunfeng Qian Shunyu Hou Jiafeng Lu Qinyan Zou Hong Li Boxian Huang |
| author_sort | Chenyue Ding |
| collection | DOAJ |
| description | Human amniotic mesenchymal stem cells (hAMSCs) were previously shown to effectively rescue ovarian function in a premature ovarian insufficiency (POI) mouse model. The therapeutic mechanism of hAMSC-derived exosomes (hAMSC-Exos) is not fully understood. In this study, the therapeutic mechanism involved in exosomal microRNA-320a (miR-320a) and Sirtuin 4 (SIRT4) was investigated in POI mouse ovaries oocytes and human granulosa cells (hGCs) by fluorescence-activated cell sorting (FACS), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence experiments. hAMSC-Exos improved proliferation, inhibited apoptosis, and decreased the expression of SIRT4 and relative genes in POI hGCs and ovaries. hAMSC-Exos elevated ovarian function and prohibited SIRT4 expression in oogenesis. The therapeutic effects were attenuated when miR-320a was knocked down. hAMSC-Exos decreased the ROS levels in POI hGCs and oocytes and improved ovarian weight and litter size, except for the Exosanti-miR-320a/POI group. Finally, hAMSC-Exos reduced the SIRT4 and ROS levels in POI ovaries and hGCs. The downstream protein expression (ANT2, AMP-dependent kinase [AMPK], and L-OPA1) was downregulated in the hGCs-SIRT4KD group but disappeared in the Exosanti-miR-320a/POI group. Our study is the first to illustrate the therapeutic potential of hAMSC-Exos in POI. Exosomal miR-320 plays a key role in the hAMSC-Exos-mediated effects on ovarian function via SIRT4 signaling. |
| first_indexed | 2024-12-11T09:24:04Z |
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| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-11T09:24:04Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
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| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-b34fb905ad06411599f7037d7aee24882022-12-22T01:13:12ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-09-01213750Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POIChenyue Ding0Chunfeng Qian1Shunyu Hou2Jiafeng Lu3Qinyan Zou4Hong Li5Boxian Huang6Center of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, ChinaCenter of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, ChinaDepartment of Obstetrics and Gynecology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215002, ChinaCenter of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, ChinaCenter of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, ChinaCenter of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China; Corresponding author: Hong Li, Center of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215002, China.Center of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China; Corresponding author: Boxian Huang, Center of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215002, China.Human amniotic mesenchymal stem cells (hAMSCs) were previously shown to effectively rescue ovarian function in a premature ovarian insufficiency (POI) mouse model. The therapeutic mechanism of hAMSC-derived exosomes (hAMSC-Exos) is not fully understood. In this study, the therapeutic mechanism involved in exosomal microRNA-320a (miR-320a) and Sirtuin 4 (SIRT4) was investigated in POI mouse ovaries oocytes and human granulosa cells (hGCs) by fluorescence-activated cell sorting (FACS), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence experiments. hAMSC-Exos improved proliferation, inhibited apoptosis, and decreased the expression of SIRT4 and relative genes in POI hGCs and ovaries. hAMSC-Exos elevated ovarian function and prohibited SIRT4 expression in oogenesis. The therapeutic effects were attenuated when miR-320a was knocked down. hAMSC-Exos decreased the ROS levels in POI hGCs and oocytes and improved ovarian weight and litter size, except for the Exosanti-miR-320a/POI group. Finally, hAMSC-Exos reduced the SIRT4 and ROS levels in POI ovaries and hGCs. The downstream protein expression (ANT2, AMP-dependent kinase [AMPK], and L-OPA1) was downregulated in the hGCs-SIRT4KD group but disappeared in the Exosanti-miR-320a/POI group. Our study is the first to illustrate the therapeutic potential of hAMSC-Exos in POI. Exosomal miR-320 plays a key role in the hAMSC-Exos-mediated effects on ovarian function via SIRT4 signaling.http://www.sciencedirect.com/science/article/pii/S2162253120301396human amniotic mesenchymal stem cellsexosomesmiR-320aSIRT4premature ovarian insufficiencyoxidative stres |
| spellingShingle | Chenyue Ding Chunfeng Qian Shunyu Hou Jiafeng Lu Qinyan Zou Hong Li Boxian Huang Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POI Molecular Therapy: Nucleic Acids human amniotic mesenchymal stem cells exosomes miR-320a SIRT4 premature ovarian insufficiency oxidative stres |
| title | Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POI |
| title_full | Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POI |
| title_fullStr | Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POI |
| title_full_unstemmed | Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POI |
| title_short | Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POI |
| title_sort | exosomal mirna 320a is released from hamscs and regulates sirt4 to prevent reactive oxygen species generation in poi |
| topic | human amniotic mesenchymal stem cells exosomes miR-320a SIRT4 premature ovarian insufficiency oxidative stres |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120301396 |
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