Synovial GATA1 mediates rheumatoid arthritis progression via transcriptional activation of NOS2 signaling.

Abstract

Transcriptional regulation of inducible nitric oxide synthase (iNOS) is critically involved in the pathogenesis and progression of rheumatoid arthritis (RA); however, the specific transcription factors that control this process remain largely unidentified. In the present study, it was discovered that expression of the key erythroid factor, globin transcription factor 1 (GATA1), is significantly greater in human RA synovial tissues than in osteoarthritis (OA) tissues. IL 6 was found to induce synovial GATA1 expression in a signal transducer and activator of transcription 3-dependent manner. Functionally, knockdown of GATA1 expression using specific small interfering RNA treatment was found to compromise immunoreaction-elicited expression of proinflammatory cytokines and thus impair invasiveness of the human fibroblast-like synovial cell line MH7A, whereas introduction of exogenous GATA1 was found to promote production of proinflammatory cytokines, leading to greater aggressiveness of MH7A cells. Mechanistically, GATA1 acts as the transcriptional coactivator of NOS2 (the gene encoding iNOS) transcription. Collectively, these data suggest that synovial GATA1 is an essential contributor to development and exacerbation of RA, presumably by inducing NOS2 transcription.

• Authors: Huan Liu, Shu-Ping Wei, Li-Qin Zhi, Li-Ping Liu, Tuan-Ping Cao, Su-Zhi Wang, Qing-Ping Chen, Dan Liu
• Journal: Microbiology and immunology (Microbiol Immunol) Vol. 62 Issue 9 Pg. 594-606 (Sep 2018) ISSN: 1348-0421 [Electronic] Australia
• PMID: 29993142 (Publication Type: Journal Article)
• Copyright: © 2018 The Societies and John Wiley & Sons Australia, Ltd.

Chemical References

• Cytokines
• GATA1 Transcription Factor
• GATA1 protein, human
• IL6 protein, human
• Interleukin-6
• STAT3 Transcription Factor
• STAT3 protein, human
• NOS2 protein, human
• Nitric Oxide Synthase Type II

Topics

• Arthritis, Rheumatoid (metabolism, pathology)
• Cell Line
• Cytokines (metabolism)
• Disease Progression
• Fibroblasts
• GATA1 Transcription Factor (genetics, metabolism)
• Gene Expression Regulation
• Humans
• Immunohistochemistry
• Interleukin-6 (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (physiology)
• Synovial Membrane (metabolism)
• Transcriptional Activation (physiology)