hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis
Mesenchymal stem cells (MSCs)-derived exosomes were considered a novel therapeutic approach in many aging-related diseases. This study aimed to clarify the protective effects of human placenta MSCs-derived exosomes (hPMSC-Exo) in aging-related CD4+ T cell senescence and identified the underlying mec...
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.780897/full |
| _version_ | 1818404271323873280 |
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| author | Yanlian Xiong Yanlei Xiong Hengchao Zhang Yaxuan Zhao Kaiyue Han Jiashen Zhang Dongmei Zhao Zhenhai Yu Ziran Geng Longfei Wang Yueming Wang Xiying Luan |
| author_facet | Yanlian Xiong Yanlei Xiong Hengchao Zhang Yaxuan Zhao Kaiyue Han Jiashen Zhang Dongmei Zhao Zhenhai Yu Ziran Geng Longfei Wang Yueming Wang Xiying Luan |
| author_sort | Yanlian Xiong |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs)-derived exosomes were considered a novel therapeutic approach in many aging-related diseases. This study aimed to clarify the protective effects of human placenta MSCs-derived exosomes (hPMSC-Exo) in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model. Senescent T cells were detected SA-β-gal stain. The degree of DNA damage was evaluated by detecting the level of 8-OH-dG. The superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities were measured. The expression of aging-related proteins and senescence-associated secretory phenotype (SASP) were detected by Western blot and RT-PCR. We found that hPMSC-Exo treatment markedly decreased oxidative stress damage (ROS and 8-OH-dG), SA-β-gal positive cell number, aging-related protein expression (p53 and γ-H2AX), and SASP expression (IL-6 and OPN) in senescent CD4+ T cells. Additionally, hPMSC-Exo containing miR-21 effectively downregulated the expression of PTEN, increased p-PI3K and p-AKT expression, and Nrf2 nuclear translocation and the expression of downstream target genes (NQO1 and HO-1) in senescent CD4+ T cells. Furthermore, in vitro studies uncovered that hPMSC-Exo attenuated CD4+ T cell senescence by improving the PTEN/PI3K-Nrf2 axis by using the PTEN inhibitor bpV (HOpic). We also validated that PTEN was a target of miR-21 by using a luciferase reporter assay. Collectively, the obtained results suggested that hPMSC-Exo attenuates CD4+ T cells senescence via carrying miRNA-21 and activating PTEN/PI3K-Nrf2 axis mediated exogenous antioxidant defenses. |
| first_indexed | 2024-12-14T08:37:30Z |
| format | Article |
| id | doaj.art-2c195ba6e0eb4fbabeb04e5b8747262a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T08:37:30Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2c195ba6e0eb4fbabeb04e5b8747262a2022-12-21T23:09:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.780897780897hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 AxisYanlian Xiong0Yanlei Xiong1Hengchao Zhang2Yaxuan Zhao3Kaiyue Han4Jiashen Zhang5Dongmei Zhao6Zhenhai Yu7Ziran Geng8Longfei Wang9Yueming Wang10Xiying Luan11Department of Anatomy, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Immunology, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Immunology, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Immunology, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Immunology, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Immunology, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Anatomy, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Anatomy, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Anatomy, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Immunology, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Immunology, School of Basic Medicine, Binzhou Medical University, Yantai, ChinaMesenchymal stem cells (MSCs)-derived exosomes were considered a novel therapeutic approach in many aging-related diseases. This study aimed to clarify the protective effects of human placenta MSCs-derived exosomes (hPMSC-Exo) in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model. Senescent T cells were detected SA-β-gal stain. The degree of DNA damage was evaluated by detecting the level of 8-OH-dG. The superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities were measured. The expression of aging-related proteins and senescence-associated secretory phenotype (SASP) were detected by Western blot and RT-PCR. We found that hPMSC-Exo treatment markedly decreased oxidative stress damage (ROS and 8-OH-dG), SA-β-gal positive cell number, aging-related protein expression (p53 and γ-H2AX), and SASP expression (IL-6 and OPN) in senescent CD4+ T cells. Additionally, hPMSC-Exo containing miR-21 effectively downregulated the expression of PTEN, increased p-PI3K and p-AKT expression, and Nrf2 nuclear translocation and the expression of downstream target genes (NQO1 and HO-1) in senescent CD4+ T cells. Furthermore, in vitro studies uncovered that hPMSC-Exo attenuated CD4+ T cell senescence by improving the PTEN/PI3K-Nrf2 axis by using the PTEN inhibitor bpV (HOpic). We also validated that PTEN was a target of miR-21 by using a luciferase reporter assay. Collectively, the obtained results suggested that hPMSC-Exo attenuates CD4+ T cells senescence via carrying miRNA-21 and activating PTEN/PI3K-Nrf2 axis mediated exogenous antioxidant defenses.https://www.frontiersin.org/articles/10.3389/fimmu.2021.780897/fullagingmiR-21Nrf2CD4 + T cellshPMSCexosomes |
| spellingShingle | Yanlian Xiong Yanlei Xiong Hengchao Zhang Yaxuan Zhao Kaiyue Han Jiashen Zhang Dongmei Zhao Zhenhai Yu Ziran Geng Longfei Wang Yueming Wang Xiying Luan hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis Frontiers in Immunology aging miR-21 Nrf2 CD4 + T cells hPMSC exosomes |
| title | hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis |
| title_full | hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis |
| title_fullStr | hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis |
| title_full_unstemmed | hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis |
| title_short | hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis |
| title_sort | hpmscs derived exosomal mirna 21 protects against aging related oxidative damage of cd4 t cells by targeting the pten pi3k nrf2 axis |
| topic | aging miR-21 Nrf2 CD4 + T cells hPMSC exosomes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.780897/full |
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