Acidosis induces synovial fibroblasts to release vascular endothelial growth factor via acid-sensitive ion channel 1a
| Autor: | Yihao Zhang, Sujing Song, Ruowen Niu, Xiaoqing Peng, Cong Wang, Xuewen Qian, Feihu Chen, Jingjing Tao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Vascular Endothelial Growth Factor A Stimulation Pathology and Forensic Medicine Small hairpin RNA Arthritis Rheumatoid Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Extracellular Gene silencing Animals Humans Molecular Biology Cells Cultured Chemistry Vascular disease Synovial Membrane Cell Biology Hydrogen-Ion Concentration medicine.disease Arthritis Experimental Synoviocytes In vitro Rats Vascular endothelial growth factor Acid Sensing Ion Channels 030104 developmental biology Cellular Microenvironment 030220 oncology & carcinogenesis Rheumatoid arthritis Cancer research Acidosis Microvascular Density |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology. 101(3) |
| ISSN: | 1530-0307 |
| Popis: | 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. Both ASIC1a and VEGF are highly expressed in rheumatoid arthritis synovial tissue and are associated with vascular disease. Interfering with ASIC1a in vitro using silencing, blocking, and overexpression interferes with the release of VEGF under acid stimulation. Blocking ASIC1a in the articular cavity of rats with adjuvant arthritis not only reduces the expression of VEGF in the synovium, but also reduces the proliferation and lesions of blood vessels and interferes with the development of the disease. |
| Databáze: | OpenAIRE |
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