Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN
Balancing hepatocyte death and proliferation is key to non-transplantation treatments for acute liver failure (ALF), which has a high short-term mortality rate. Small extracellular vesicles (sEVs) may act as mediators in the repair of damaged liver tissue by mesenchymal stem cells (MSCs). We aimed t...
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| Format: | Article |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1168545/full |
| _version_ | 1827941609296101376 |
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| author | Jing Zhang Jing Zhang Juan Gao Juan Gao Xianlong Li Dengna Lin Zhihui Li Jialei Wang Jialei Wang Junfeng Chen Zhiliang Gao Bingliang Lin Bingliang Lin |
| author_facet | Jing Zhang Jing Zhang Juan Gao Juan Gao Xianlong Li Dengna Lin Zhihui Li Jialei Wang Jialei Wang Junfeng Chen Zhiliang Gao Bingliang Lin Bingliang Lin |
| author_sort | Jing Zhang |
| collection | DOAJ |
| description | Balancing hepatocyte death and proliferation is key to non-transplantation treatments for acute liver failure (ALF), which has a high short-term mortality rate. Small extracellular vesicles (sEVs) may act as mediators in the repair of damaged liver tissue by mesenchymal stem cells (MSCs). We aimed to investigate the efficacy of human bone marrow MSC-derived sEVs (BMSC-sEVs) in treating mice with ALF and the molecular mechanisms involved in regulating hepatocyte proliferation and apoptosis. Small EVs and sEV-free BMSC concentrated medium were injected into mice with LPS/D-GalN-induced ALF to assess survival, changes in serology, liver pathology, and apoptosis and proliferation in different phases. The results were further verified in vitro in L-02 cells with hydrogen peroxide injury. BMSC-sEV-treated mice with ALF had higher 24 h survival rates and more significant reductions in liver injury than mice treated with sEV-free concentrated medium. BMSC-sEVs reduced hepatocyte apoptosis and promoted cell proliferation by upregulating miR-20a-5p, which targeted the PTEN/AKT signaling pathway. Additionally, BMSC-sEVs upregulated the mir-20a precursor in hepatocytes. The application of BMSC-sEVs showed a positive impact by preventing the development of ALF, and may serve as a promising strategy for promoting ALF liver regeneration. miR-20a-5p plays an important role in liver protection from ALF by BMSC-sEVs. |
| first_indexed | 2024-03-13T09:43:15Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-13T09:43:15Z |
| publishDate | 2023-05-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-2bf06c17e4f5403f938eac76fc65ce752023-05-25T04:23:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.11685451168545Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTENJing Zhang0Jing Zhang1Juan Gao2Juan Gao3Xianlong Li4Dengna Lin5Zhihui Li6Jialei Wang7Jialei Wang8Junfeng Chen9Zhiliang Gao10Bingliang Lin11Bingliang Lin12Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaGuangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaGuangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaGuangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, ChinaBalancing hepatocyte death and proliferation is key to non-transplantation treatments for acute liver failure (ALF), which has a high short-term mortality rate. Small extracellular vesicles (sEVs) may act as mediators in the repair of damaged liver tissue by mesenchymal stem cells (MSCs). We aimed to investigate the efficacy of human bone marrow MSC-derived sEVs (BMSC-sEVs) in treating mice with ALF and the molecular mechanisms involved in regulating hepatocyte proliferation and apoptosis. Small EVs and sEV-free BMSC concentrated medium were injected into mice with LPS/D-GalN-induced ALF to assess survival, changes in serology, liver pathology, and apoptosis and proliferation in different phases. The results were further verified in vitro in L-02 cells with hydrogen peroxide injury. BMSC-sEV-treated mice with ALF had higher 24 h survival rates and more significant reductions in liver injury than mice treated with sEV-free concentrated medium. BMSC-sEVs reduced hepatocyte apoptosis and promoted cell proliferation by upregulating miR-20a-5p, which targeted the PTEN/AKT signaling pathway. Additionally, BMSC-sEVs upregulated the mir-20a precursor in hepatocytes. The application of BMSC-sEVs showed a positive impact by preventing the development of ALF, and may serve as a promising strategy for promoting ALF liver regeneration. miR-20a-5p plays an important role in liver protection from ALF by BMSC-sEVs.https://www.frontiersin.org/articles/10.3389/fphar.2023.1168545/fullacute liver failureextracellular vesiclesliver regenerationmesenchymal stem cellsmiRNA |
| spellingShingle | Jing Zhang Jing Zhang Juan Gao Juan Gao Xianlong Li Dengna Lin Zhihui Li Jialei Wang Jialei Wang Junfeng Chen Zhiliang Gao Bingliang Lin Bingliang Lin Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN Frontiers in Pharmacology acute liver failure extracellular vesicles liver regeneration mesenchymal stem cells miRNA |
| title | Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN |
| title_full | Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN |
| title_fullStr | Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN |
| title_full_unstemmed | Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN |
| title_short | Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN |
| title_sort | bone marrow mesenchymal stem cell derived small extracellular vesicles promote liver regeneration via mir 20a 5p pten |
| topic | acute liver failure extracellular vesicles liver regeneration mesenchymal stem cells miRNA |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1168545/full |
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