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Apelin 通过 miR-525-5p/Angiopoietin-1 通路促进类风湿关节炎疾病中的内皮祖细胞血管生成。

Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease the miR-525-5p/Angiopoietin-1 Pathway.

机构信息

Department of Medicine, Mackay Medical College, New Taipei, Taiwan.

Division of Spine Surgery, Department of Orthopedic Surgery, MacKay Memorial Hospital, New Taipei, Taiwan.

出版信息

Front Immunol. 2021 Sep 29;12:737990. doi: 10.3389/fimmu.2021.737990. eCollection 2021.

DOI:10.3389/fimmu.2021.737990
PMID:34659230
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8511637/
Abstract

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 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.

摘要

血管生成是新毛细血管形成的关键过程，也是类风湿关节炎 (RA) 发病机制的关键参与者。脂肪因子 Apelin (APLN) 在包括血管生成在内的几种细胞功能中发挥关键作用。我们报告称，APLN 处理 RA 滑膜成纤维细胞 (RASFs) 会增加血管生成素 1 (Ang1) 的表达。Ang1 抗体可消除 APLN 处理的 RASFs 条件培养基中内皮祖细胞 (EPC) 的管状形成和迁移。我们还发现，与骨关节炎患者相比，RA 患者的滑液中 APLN 和 Ang1 的表达水平明显更高。APLN 通过抑制 miR-525-5p 的合成磷脂酶 C 伽马 (PLCγ) 和蛋白激酶 Cα (PKCα) 信号通路，促进 Ang1 依赖性 EPC 血管生成。重要的是，APLN shRNA 的感染减轻了胶原诱导性关节炎小鼠踝关节中 EPC 血管生成、关节肿胀和软骨侵蚀。因此，APLN 是 RA 的一种新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e0/8511637/dd5a4fc6ed85/fimmu-12-737990-g007.jpg
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