A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis

Abstract As a transcription factor, E2F2 participates in regulation of numerous genes. To investigate the role and mechnism of E2F2 in RA, expression of E2F2 in synovial tissue was detected. Proliferation, invasion, and secretion of inflammatory cytokines were measured after E2F2 was knocked-down in...

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Autores principales:	Rui Zhang, Lin Wang, Ji-hong Pan, Jinxiang Han
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80c4356019144a4f879bb6f6b36566df
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spelling	oai:doaj.org-article:80c4356019144a4f879bb6f6b36566df2021-12-02T15:09:10ZA critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis10.1038/s41598-018-20782-72045-2322https://doaj.org/article/80c4356019144a4f879bb6f6b36566df2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20782-7https://doaj.org/toc/2045-2322Abstract As a transcription factor, E2F2 participates in regulation of numerous genes. To investigate the role and mechnism of E2F2 in RA, expression of E2F2 in synovial tissue was detected. Proliferation, invasion, and secretion of inflammatory cytokines were measured after E2F2 was knocked-down in RASFs by siRNA transfection. Induction of TNF-α, IL-6, and LPS on expression and nuclear translocation of E2F2, and signal pathways involved in the process were tested. ChIP was used to investigate direct binding of NF-кB to the promoter of E2F2, and E2F2 to the promoter of IL-6. The correlation between mRNA levels of E2F2 and IL-6 or TNF-α in secreted in supernatant of RASFs were also investigated. As a result, silencing E2F2 could inhibit the proliferation and invasion of RASFs. LPS, IL-6 can stimulate the expression of E2F2 in RASFs both via the NF-кB pathway, while TNF-α via the ERK pathway. TNF-α can facilitate the nuclear translocation of E2F2 and TNF-α can bind to promoter of E2F2, and then E2F2 can bind to the promoter of IL-6 directly. Significant correlations was found between levels of E2F2 and IL-6/TNF-α in synoviocytes of RA patients. Our findings indicate that E2F2 may play an important role in pathogenesis of RA.Rui ZhangLin WangJi-hong PanJinxiang HanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rui Zhang Lin Wang Ji-hong Pan Jinxiang Han A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis
description	Abstract As a transcription factor, E2F2 participates in regulation of numerous genes. To investigate the role and mechnism of E2F2 in RA, expression of E2F2 in synovial tissue was detected. Proliferation, invasion, and secretion of inflammatory cytokines were measured after E2F2 was knocked-down in RASFs by siRNA transfection. Induction of TNF-α, IL-6, and LPS on expression and nuclear translocation of E2F2, and signal pathways involved in the process were tested. ChIP was used to investigate direct binding of NF-кB to the promoter of E2F2, and E2F2 to the promoter of IL-6. The correlation between mRNA levels of E2F2 and IL-6 or TNF-α in secreted in supernatant of RASFs were also investigated. As a result, silencing E2F2 could inhibit the proliferation and invasion of RASFs. LPS, IL-6 can stimulate the expression of E2F2 in RASFs both via the NF-кB pathway, while TNF-α via the ERK pathway. TNF-α can facilitate the nuclear translocation of E2F2 and TNF-α can bind to promoter of E2F2, and then E2F2 can bind to the promoter of IL-6 directly. Significant correlations was found between levels of E2F2 and IL-6/TNF-α in synoviocytes of RA patients. Our findings indicate that E2F2 may play an important role in pathogenesis of RA.
format	article
author	Rui Zhang Lin Wang Ji-hong Pan Jinxiang Han
author_facet	Rui Zhang Lin Wang Ji-hong Pan Jinxiang Han
author_sort	Rui Zhang
title	A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis
title_short	A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis
title_full	A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis
title_fullStr	A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis
title_full_unstemmed	A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis
title_sort	critical role of e2f transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid arthritis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/80c4356019144a4f879bb6f6b36566df
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A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis

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