To investigate the expression of hypoxia inducible factor (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in the synovium of collagen-induced arthritis (CIA) joint, and whether the PI3K pathway regulates angiogenesis in rheumatoid arthritis or not. A randomized controlled according to the principle of the rats were divided into normal control group (10 rats) and the experimental group (40 rats). The experimental group rats were established as type II collagen plus adjuvant Freund's complete adjuvant-induced arthritis model. HIF-1 alpha and VEGF proteins' expression in serum of CIA rats group and normal control group were detected by ELISA. Microvessel density (MVD) in synovial tissue of CIA rats group and normal control group were detected by immunohistochemistry (IHC) staining. The protein expression of PTEN, PI3K, and AKT in synovial tissue were detected by Western Blot. Compared with normal control group, toes and ankle swelling and arthritis index (AI) of CIA rat increased, and the expression of VEGF and HIF-1 alpha proteins in peripheral serum increased, IHC showed that MVD was significantly higher than that of the control group, and the difference was statistically significant (p< 0.05). Western Blot results showed that PI3K and AKT proteins expression in CIA synovial tissue of rats increased, while the expression of PTEN protein decreased. Correlation analysis showed that VEGF and HIF-1 levels in the peripheral serum of CIA rats were positively correlated with arthritis index (AI); the contents of HIF-1 alpha and VEGF in the peripheral serum of CIA rats were positively correlated with MVD in synovium tissue. The CIA rat model regulated the expression of HIF-1 alpha and VEGF proteins in peripheral serum by PI3K signaling pathway, and then regulated neovascularization in RA.
机构:
Univ Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Div Hematol & Oncol, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Div Hematol & Oncol, Dallas, TX 75390 USA
Sadeghi, Navid
Gerber, David E.
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Univ Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Div Hematol & Oncol, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Div Hematol & Oncol, Dallas, TX 75390 USA
机构:
Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, EnglandGuys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England
Papadatos-Pastos, Dionysios
Rabbie, Roy
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Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, EnglandGuys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England
Rabbie, Roy
Ross, Paul
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Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, EnglandGuys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England
Ross, Paul
Sarker, Debashis
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Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England
Kings Coll London, Dept Res Oncol, Div Canc Studies, London WC2R 2LS, EnglandGuys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England