hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis
| Autor: | Yueming Wang, Yanlei Xiong, Dongmei Zhao, Kaiyue Han, Zhenhai Yu, Xiying Luan, Longfei Wang, Jiashen Zhang, Hengchao Zhang, Yaxuan Zhao, Yanlian Xiong, Ziran Geng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Senescence
hPMSC biology Chemistry DNA damage T cell aging Immunology Mesenchymal stem cell exosomes RC581-607 medicine.disease_cause Nrf2 Cell biology Superoxide dismutase medicine.anatomical_structure CD4 + T cells biology.protein medicine Immunology and Allergy PTEN miR-21 Immunologic diseases. Allergy PI3K/AKT/mTOR pathway Oxidative stress |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.780897 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|