Acidosis induces synovial fibroblasts to release vascular endothelial growth factor via acid-sensitive ion channel 1a
Acidosis induces synovial fibroblasts to release vascular endothelial growth factor via acid-sensitive ion channel 1a
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酸中毒诱导滑膜成纤维细胞通过酸敏感离子通道1a释放血管内皮生长因子
DOI：
10.1038/s41374-020-0423-6
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发表时间：
2020-08
影响因子：
5
通讯作者：
Feihu Chen
中科院分区：
文献类型：
--
作者：
Xuewen Qian;Yihao Zhang;Jingjing Tao;Ruowen Niu;Sujing Song;Cong Wang;Xiaoqing Peng;Feihu Chen
酸敏离子通道1a(ASIC1a)是细胞外H+激活的阳离子通道家族的成员。研究表明，组织酸化有助于类风湿关节炎(RA)滑膜组织中微血管的形成，但其潜在机制尚不清楚。本研究旨在探讨组织酸化在关节炎滑膜组织微血管形成中的作用，以及ASIC1a对关节炎滑膜组织释放血管内皮生长因子(VEGF)的影响。结果表明，在RA滑膜组织和佐剂性关节炎(AA)大鼠滑膜组织中，ASIC1a表达、VEGF表达和微血管密度(MVD)均升高。应用ASIC1a特异性阻滞剂PcTx-1治疗后，AA大鼠脑内ASIC1a表达、血管内皮细胞生长因子表达及微血管密度均降低。酸化RA滑膜成纤维细胞(RASF)可促进血管内皮细胞生长因子的释放。PcTx-1和ASIC1a-短发夹状RNA可抑制酸诱导的血管内皮生长因子的释放。此外，ASIC1a过表达载体还能促进酸诱导的血管内皮细胞生长因子释放。这表明胞外酸化通过ASIC1a诱导RASF释放血管内皮生长因子。这些发现提示，阻断ASIC1a介导滑膜细胞释放血管内皮生长因子可能为RA的治疗提供一种潜在的治疗策略。
Acid-sensitive ion channel 1a (ASIC1a) is a member of the extracellular H+ activated cation channel family. Studies have shown that tissue acidification contributes to the formation of microvessels in rheumatoid arthritis (RA) synovial tissue, but its underlying mechanisms remain unclear. The purpose of this study was to investigate the role of tissue acidification in microvascular formation of arthritic synovial tissue and the effect of ASIC1a on vascular endothelial growth factor (VEGF) release from arthritic synovial tissue. Our results indicate that ASIC1a expression, VEGF expression, and microvessel density (MVD) are elevated in RA synovial tissue and adjuvant arthritis (AA) rat synovial tissue. When AA rats were treated with ASIC1a-specific blocker psalmotoxin-1 (PcTx-1), the expression of ASIC1a, VEGF expression, and MVD were all reduced. Acidification of RA synovial fibroblasts (RASF) can promote the release of VEGF. PcTx-1 and ASIC1a-short hairpin RNA can inhibit acid-induced release of VEGF. In addition, the ASIC1a overexpression vector can promote acid-induced VEGF release. This indicates that extracellular acidification induces the release of VEGF by RASF via ASIC1a. These findings suggest that blocking ASIC1a mediates the release of VEGF from synoviocytes may provide a potential therapeutic strategy for RA therapy.
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DOI：
10.7150/thno.37200
发表时间：
2020-01
期刊：
Ivyspring International Publisher
影响因子：
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发表时间：
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发表时间：
2009-10
期刊：
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DOI：
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发表时间：
2014-11-01
影响因子：
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