Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway
Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The adipokine apelin (APLN) plays critical roles in several cellular functions, including angiogenesis. We report that APLN treatment of RA synovial fibroblasts (RA...
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| Format: | Article |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.737990/full |
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| author | Ting-Kuo Chang Ting-Kuo Chang You-Han Zhong Shan-Chi Liu Chien-Chung Huang Chien-Chung Huang Chun-Hao Tsai Chun-Hao Tsai Hsiang-Ping Lee Hsiang-Ping Lee Shih-Wei Wang Shih-Wei Wang Shih-Wei Wang Chin-Jung Hsu Chin-Jung Hsu Chih-Hsin Tang Chih-Hsin Tang Chih-Hsin Tang Chih-Hsin Tang |
| author_facet | Ting-Kuo Chang Ting-Kuo Chang You-Han Zhong Shan-Chi Liu Chien-Chung Huang Chien-Chung Huang Chun-Hao Tsai Chun-Hao Tsai Hsiang-Ping Lee Hsiang-Ping Lee Shih-Wei Wang Shih-Wei Wang Shih-Wei Wang Chin-Jung Hsu Chin-Jung Hsu Chih-Hsin Tang Chih-Hsin Tang Chih-Hsin Tang Chih-Hsin Tang |
| author_sort | Ting-Kuo Chang |
| collection | DOAJ |
| description | Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The adipokine apelin (APLN) plays critical roles in several cellular functions, including angiogenesis. We report that APLN treatment of RA synovial fibroblasts (RASFs) increased angiopoietin-1 (Ang1) expression. Ang1 antibody abolished endothelial progenitor cell (EPC) tube formation and migration in conditioned medium from APLN-treated RASFs. We also found significantly higher levels of APLN and Ang1 expression in synovial fluid from RA patients compared with those with osteoarthritis. APLN facilitated Ang1-dependent EPC angiogenesis by inhibiting miR-525-5p synthesis via phospholipase C gamma (PLCγ) and protein kinase C alpha (PKCα) signaling. Importantly, infection with APLN shRNA mitigated EPC angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with collagen-induced arthritis. APLN is therefore a novel therapeutic target for RA. |
| first_indexed | 2024-12-14T17:11:00Z |
| format | Article |
| id | doaj.art-8ad9dd7a417146e088a0b9eb0e8dd3ee |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T17:11:00Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8ad9dd7a417146e088a0b9eb0e8dd3ee2022-12-21T22:53:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.737990737990Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 PathwayTing-Kuo Chang0Ting-Kuo Chang1You-Han Zhong2Shan-Chi Liu3Chien-Chung Huang4Chien-Chung Huang5Chun-Hao Tsai6Chun-Hao Tsai7Hsiang-Ping Lee8Hsiang-Ping Lee9Shih-Wei Wang10Shih-Wei Wang11Shih-Wei Wang12Chin-Jung Hsu13Chin-Jung Hsu14Chih-Hsin Tang15Chih-Hsin Tang16Chih-Hsin Tang17Chih-Hsin Tang18Department of Medicine, Mackay Medical College, New Taipei, TaiwanDivision of Spine Surgery, Department of Orthopedic Surgery, MacKay Memorial Hospital, New Taipei, TaiwanGraduate Institute of Biomedical Science, China Medical University, Taichung, TaiwanDepartment of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, TaiwanSchool of Medicine, China Medical University, Taichung, TaiwanDivision of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, TaiwanDepartment of Sports Medicine, College of Health Care, China Medical University, Taichung, TaiwanDepartment of Orthopedic Surgery, China Medical University Hospital, Taichung, TaiwanSchool of Chinese Medicine, China Medical University, Taichung, Taiwan0Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan1Department of Medicine, MacKay Medical College, New Taipei City, Taiwan2Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan3Institute of Biomedical Sciences, Mackay Medical College, Taipei, TaiwanDepartment of Orthopedic Surgery, China Medical University Hospital, Taichung, TaiwanSchool of Chinese Medicine, China Medical University, Taichung, TaiwanGraduate Institute of Biomedical Science, China Medical University, Taichung, TaiwanSchool of Medicine, China Medical University, Taichung, Taiwan4Chinese Medicine Research Center, China Medical University, Taichung, Taiwan5Department of Biotechnology, College of Health Science, Asia University, Taichung, TaiwanAngiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The adipokine apelin (APLN) plays critical roles in several cellular functions, including angiogenesis. We report that APLN treatment of RA synovial fibroblasts (RASFs) increased angiopoietin-1 (Ang1) expression. Ang1 antibody abolished endothelial progenitor cell (EPC) tube formation and migration in conditioned medium from APLN-treated RASFs. We also found significantly higher levels of APLN and Ang1 expression in synovial fluid from RA patients compared with those with osteoarthritis. APLN facilitated Ang1-dependent EPC angiogenesis by inhibiting miR-525-5p synthesis via phospholipase C gamma (PLCγ) and protein kinase C alpha (PKCα) signaling. Importantly, infection with APLN shRNA mitigated EPC angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with collagen-induced arthritis. APLN is therefore a novel therapeutic target for RA.https://www.frontiersin.org/articles/10.3389/fimmu.2021.737990/fullapelinangiopoietin-1endothelial progenitor cells (EPC)rheumatoid arthritismiR-525-5p |
| spellingShingle | Ting-Kuo Chang Ting-Kuo Chang You-Han Zhong Shan-Chi Liu Chien-Chung Huang Chien-Chung Huang Chun-Hao Tsai Chun-Hao Tsai Hsiang-Ping Lee Hsiang-Ping Lee Shih-Wei Wang Shih-Wei Wang Shih-Wei Wang Chin-Jung Hsu Chin-Jung Hsu Chih-Hsin Tang Chih-Hsin Tang Chih-Hsin Tang Chih-Hsin Tang Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway Frontiers in Immunology apelin angiopoietin-1 endothelial progenitor cells (EPC) rheumatoid arthritis miR-525-5p |
| title | Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway |
| title_full | Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway |
| title_fullStr | Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway |
| title_full_unstemmed | Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway |
| title_short | Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway |
| title_sort | apelin promotes endothelial progenitor cell angiogenesis in rheumatoid arthritis disease via the mir 525 5p angiopoietin 1 pathway |
| topic | apelin angiopoietin-1 endothelial progenitor cells (EPC) rheumatoid arthritis miR-525-5p |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.737990/full |
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