Rac1 regulates platelet microparticles formation and rheumatoid arthritis deterioration
Platelets play important roles in blood clotting, hemostasis and wound repair, while more and more research show that platelets also have significant contributions in the process of inflammation. Rheumatoid arthritis is a chronic systemic inflammatory autoimmune disease. Platelet microparticles, whi...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Platelets |
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| Online Access: | http://dx.doi.org/10.1080/09537104.2019.1584669 |
| Summary: | Platelets play important roles in blood clotting, hemostasis and wound repair, while more and more research show that platelets also have significant contributions in the process of inflammation. Rheumatoid arthritis is a chronic systemic inflammatory autoimmune disease. Platelet microparticles, which are membrane vesicles shed by activated platelets, are reported to amplify inflammation in Rheumatoid arthritis. Here we show that either platelet-specific deletion of Rac1 (Rac1−/-) or Rac1-specific inhibitor NSC23766 dramatically inhibit platelet-derived microparticles formation. As we all know, collagen-induced arthritis (CIA) mouse model is the most common autoimmune model of rheumatoid arthritis. Interestingly, NSC23766 alleviated the process of collagen-induced arthritis of DBA mice in vivo, including the reduced hind paw thickness and ankle stiffness, the reduction of arthritic scores and incidence of arthritis. Our work also found that NSC23766-treated CIA mouse spleen is less swollen and contains less enlarged white pulp than PBS control. The histological analysis shows that NSC23766-treated but not solvent control improve the cartilage erosion symptom in the joint of CIA mouse. Interestingly, platelet microparticles in the peripheral blood of NSC23766-treated CIA mice were decreased significantly compared with PBS-treated CIA mice. In conclusion, our work demonstrated that Rac1 inhibition alleviates collagen-induced arthritis through the decrease of platelet microparticles’ release. In short, Rac1 aggravate the rheumatoid arthritis deterioration through the regulation of platelet microparticles formation. |
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| ISSN: | 0953-7104 1369-1635 |