Matrine inhibits synovial angiogenesis in collagen-induced arthritis rats by regulating HIF-VEGF-Ang and inhibiting the PI3K/Akt signaling pathway
| Autor: | Limei Ao, Shimin Liu, Lifen Jia, Jie Guo, Han Gao, Qiumei Dong, Bingzhen Liu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Angiogenesis medicine.medical_treatment Immunology Arthritis Neovascularization Rats Sprague-Dawley Phosphatidylinositol 3-Kinases Alkaloids medicine Basic Helix-Loop-Helix Transcription Factors Human Umbilical Vein Endothelial Cells Animals Humans Matrines Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Cells Cultured Neovascularization Pathologic Akt/PKB signaling pathway Chemistry Growth factor Synovial Membrane Ribonuclease Pancreatic medicine.disease Arthritis Experimental Synoviocytes Rats Synovial Cell Cancer research Collagen medicine.symptom Proto-Oncogene Proteins c-akt Quinolizines Signal Transduction |
| Zdroj: | Molecular immunology. 141 |
| ISSN: | 1872-9142 |
| Popis: | Matrine (Mat) is an alkaloid of tetracycline quinazine, and previous studies have demonstrated its specific effect on relieving rheumatoid arthritis (RA). However, the effect of Mat on joint synovial angiogenesis in the pathogenesis of RA has not been elucidated. In this study, body weight, joint swelling, arthritis index (AI) score, histopathological changes, immunohistochemical, and western blot- were used in collagen-induced arthritis (CIA) rats to detect pro-inflammatory factors and, - expression levels of key cytokines and proteins along the hypoxia-inducible factor (HIF)-endothelial growth factor (VEGF)-angiopoietin (Ang) axis and VEGF-phosphoinositide 3-kinase (PI3K) / protein kinase B (Akt) pathway. In vitro experiments were conducted to observe the effect of Mat on the proliferation, migration and lumen formation of RA-fibroblast-like synovial cells (FLS) and human umbilical vein endothelial cells (HUVECs). Results showed that Mat reduced the degree of paw swelling and AI score in CIA rats, joint synovial tissue proliferation, inflammatory cell infiltration, and neovascularization; moreover, it down-regulated the expression levels of inflammatory factors interleukin-1β, interferon-γ, and pro-angiogenic factors VEGF, placental growth factor, HIF-α, Ang-1, Ang-2, Tie-2, and phosphorylation-Akt in the ankle joint of CIA rats. In addition, the in vitro experiments showed that Mat inhibited the proliferation and migration of RA-FLS and inhibited the proliferation and lumen formation of HUVECs. Therefore, Mat exerts an anti-angiogenesis effect by regulating the HIF-VEGF-Ang axis and inhibiting the PI3K/Akt signaling pathway. This inhibits the pathogenesis and improve the symptoms of RA, and may be offered as a candidate drug for the treatment of RA. |
| Databáze: | OpenAIRE |
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