Inhibition of angiogenesis by arsenic trioxide via TSP-1-TGF-β1-CTGF-VEGF functional module in rheumatoid arthritis

Oncotarget
Juan ZhangZhiyi Zhang

Abstract

Angiogenesis is a critical factor for rheumatoid arthritis (RA). Although anti-TNF biologics work effectively on some RA patients, concerns have been raised about the possible increased development of malignancies alongside such treatments. Arsenic trioxide (As2O3) has attracted worldwide attention and has been reported to treat some cancers. However, the effects of As2O3 on angiogenesis in the RA synovium remain unclear. Here, we report a systematic increased expression of TSP-1, TGF-β1, CTGF and VEGF in supernatants of a RA fibroblast-like synoviocytes (RA-FLS) and human dermal microvascular endothelial cells (HDMECs) co-culture compared with those from a normal human fibroblast-like synoviocytes (NH-FLS) and HDMECs co-culture. This increased expression may up-regulate endothelial tube formation and transwell migration, as well as microvessel sprouting in ex vivo aortic ring assay. These networked angiogenic factors mainly form a functional module regulating angiogenesis in the RA synovium. We show that As2O3 inhibits angiogenesis in the collagen-induced arthritis (CIA) synovium and consequently arthritis severity via significant suppression of TSP-1, TGF-β1, CTGF and VEGF expression in the CIA synovium, plus in the RA-FLS an...Continue Reading

References

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Citations

Jul 25, 2019·Journal of Cellular Physiology·Yuhong ChenHong Zhang
Nov 9, 2019·Archives of Pharmacal Research·Juan ZhangZhiyi Zhang
Jul 12, 2019·Immunologic Research·Huijun LaiJing Sun
Apr 10, 2018·Inflammation·Juan ZhangZhiyi Zhang
Feb 17, 2021·Journal of Biochemical and Molecular Toxicology·Zhuo SunYongping Wu

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Methods Mentioned

BETA
ELISA
PCR
transfection
electrophoresis

Software Mentioned

SPSS

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