CD147 induces angiogenesis through a vascular endothelial growth factor and hypoxia-inducible transcription factor 1α-mediated pathway in rheumatoid arthritis

Aim. To analyze polymorphism in the regulatory regions of the vascular endothelial growth factor (VEGF) gene in female patients with rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 257 female patients with RA. A control group consisted of 297 women without chronic diseases. The investigators examined the single-nucleotide polymorphism of VEGF-А2578С in the promoter region (rs699947) and that of VEGF+С936Т 3 in the retranslated region (rs3025039) of the gene. Genotyping was performed by restriction fragment length polymorphism analysis. Results. There was an increase in the frequency of VEGF+936 CT and a reduction in that of the VEGF+936СС genotypes in the seronegative patients as compared to the healthy women. The VEGF+936СС genotype frequency was higher in the patients with seropositive RA than in the subgroup of seronegative patients. The frequency of the VEGF-2578СС genotype was increased in the patients with RA and rheumatoid nodules, as compared to the healthy women. Conclusion. The data presented suggest that the presence of certain VEGF gene variants located in the regulatory regions may reflect the nature of immunopathological mechanisms in RA.

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Apatinib Inhibits Angiogenesis in Intrahepatic Cholangiocarcinoma by Regulating the Vascular Endothelial Growth Factor Receptor-2/Signal Transducer and Activator of Transcription Factor 3/Hypoxia Inducible Factor 1 Subunit Alpha Signaling Axis

Pharmacology ◽

10.1159/000514410 ◽

2021 ◽

pp. 1-11

Author(s):

Man-Ping Huang ◽

Shan-Zhi Gu ◽

Bin Huang ◽

Guo-Wen Li ◽

Zheng-Ping Xiong ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Transcription Factor ◽

Growth Factor ◽

Intrahepatic Cholangiocarcinoma ◽

Hypoxia Inducible Factor ◽

Growth Factor Receptor ◽

Vascular Endothelial ◽

Signal Transducer ◽

Hypoxia Inducible Factor 1 ◽

Endothelial Growth Factor

Introduction: Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of eﬀective treatment, has risen over the past decades but without much improvement in prognosis. Objective: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. Methods: MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. Results: We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. Conclusions: Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.

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Inhibitory effect of bucillamine on the vascular endothelial growth factor in cultured synovial cells from patients with rheumatoid arthritis

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)40748-8 ◽

1998 ◽

Vol 76 ◽

pp. 160

Author(s):

Hiroyuki Aono ◽

Miwa Takai ◽

Masakazu Nagashima ◽

Shinichi Yoshino ◽

Minoru Sasano

Keyword(s):

Rheumatoid Arthritis ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Inhibitory Effect ◽

Synovial Cells ◽

Vascular Endothelial ◽

Endothelial Growth Factor

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Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy

Modern Rheumatology ◽

10.3109/s10165-008-0125-1 ◽

2009 ◽

Vol 19 (1) ◽

pp. 12-19 ◽

Cited By ~ 197

Author(s):

Norihiro Nishimoto ◽

Nobuyuki Miyasaka ◽

Kazuhiko Yamamoto ◽

Shinichi Kawai ◽

Tsutomu Takeuchi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Disease Activity ◽

Inadequate Response ◽

Vascular Endothelial ◽

Receptor Inhibition ◽

Endothelial Growth Factor ◽

Tocilizumab Monotherapy

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Clinical Significance of Serum Levels of Vascular Endothelial Growth Factor, Angiopoietin-1, and Angiopoietin-2 in Patients with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.090941 ◽

2010 ◽

Vol 37 (6) ◽

pp. 1121-1128 ◽

Cited By ~ 44

Author(s):

DAITARO KUROSAKA ◽

KENICHIRO HIRAI ◽

MAKIKO NISHIOKA ◽

YUKIO MIYAMOTO ◽

KEN YOSHIDA ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Serum Levels ◽

Vascular Endothelial ◽

Angiopoietin 2 ◽

Serum Crp ◽

Endothelial Growth Factor ◽

Vegf Level ◽

Angiopoietin 1

Objective.To evaluate the clinical significance of serum levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) in patients with rheumatoid arthritis (RA).Methods.The subjects were 70 patients with RA. Serum VEGF, Ang-1, and Ang-2 levels were determined by ELISA. As indices of disease activity, serum levels of C-reactive protein (CRP) and matrix metalloprotease (MMP)-3 were examined, and the 28-joint count Disease Activity Score (DAS28)-CRP was calculated. Power Doppler ultrasonography was performed in the bilateral wrists, elbows, shoulders, knees and ankles. The synovial blood flow signals were scored using a 3-grade scale (0–2), and the total of the scores in the 10 joints was regarded as the total signal score (TSS).Results.Serum VEGF level showed significant correlations with serum CRP and MMP-3 levels, DAS28-CRP, and TSS. Serum Ang-1 level showed significant correlations with serum MMP-3 level and DAS28-CRP. Serum Ang-2 level showed significant correlations with serum CRP level and TSS.Conclusion.The serum VEGF level is important as an index of the activity of RA based on angiogenesis and a prognostic factor regarding joint destruction. Serum Ang-1 level may be useful as an index of sustained arthritis based on the maintenance of newly formed vessels. Serum Ang-2 level may reflect a state of marked angiogenesis.

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