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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Frontiers Media S.A.
2021
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oai:doaj.org-article:2c195ba6e0eb4fbabeb04e5b8747262a2021-11-30T12:28:32ZhPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis1664-322410.3389/fimmu.2021.780897https://doaj.org/article/2c195ba6e0eb4fbabeb04e5b8747262a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.780897/fullhttps://doaj.org/toc/1664-3224Mesenchymal 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.Yanlian XiongYanlei XiongHengchao ZhangYaxuan ZhaoKaiyue HanJiashen ZhangDongmei ZhaoZhenhai YuZiran GengLongfei WangYueming WangXiying LuanFrontiers Media S.A.articleagingmiR-21Nrf2CD4 + T cellshPMSCexosomesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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| collection |
DOAJ |
| language |
EN |
| topic |
aging miR-21 Nrf2 CD4 + T cells hPMSC exosomes Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
aging miR-21 Nrf2 CD4 + T cells hPMSC exosomes Immunologic diseases. Allergy RC581-607 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
hpmscs-derived exosomal mirna-21 protects against aging-related oxidative damage of cd4+ t cells by targeting the pten/pi3k-nrf2 axis |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/2c195ba6e0eb4fbabeb04e5b8747262a |
| work_keys_str_mv |
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| _version_ |
1718406611422150656 |