title: Metastasis-associated protein 1 (MTA1) signaling in rheumatoid synovium: Regulation of inflammatory response and cytokine-mediated production of prostaglandin E2 (PGE2).
abstract: Abnormal perpetual inflammatory response and sequential cytokine-induced prostaglandin E2 (PGE2) play important roles in the pathogenesis of rheumatoid arthritis (RA). The underlying regulatory mechanism, however, remain largely unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), an important chromatin modifier that plays a critical role in transcriptional regulation by modifying DNA accessibility for cofactors, was upregulated in human rheumatoid synovial tissues. Furthermore, a knockdown of MTA1 by siRNA in the human fibroblast-like synovial cell line MH7A was found to impair the 4-hydroxynonenal (4-HNE)-induced transcriptional expression levels of certain proinflammatory cytokines including IL-1β, TNF-α and IL-6. Moreover, endogenous MTA1 was required for the cytokines-induced PGE2 synthesis by rheumatoid synoviocytes. Collectively, the coordinated existence of MTA1 inside distinct cascade loops points to its indispensable role in the modulation of the integrated cytokine network along the pathogenesis of RA. Further exploration of the functional details of this master transcriptional regulator should be an attractive strategy to identify novel therapeutic target for RA and warrants execution.
authors.affiliation: Department of Medical Psychology, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xian Yang Central Hospital, Xian Yang, 712000, China.
authors.forename: Bing-Wei
authors.initials: BW
authors.lastname: Dong
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Zheng
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Zhen-Biao
authors.initials: ZB
authors.lastname: Wu
authors.affiliation: Department of Histology and Embryology, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: liweipepeyato@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: dingjin@fmmu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Ding
mesh_terms: D000447:Aldehydes / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology*; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015534:Trans-Activators
chemical_list: D000447:Aldehydes; D016207:Cytokines; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases; C027576:4-hydroxy-2-nonenal; D015232:Dinoprostone
keywords: Cytokine; Inflammation; MH7A; Metastasis associated protein 1 (MTA1); NF-κB; Rheumatoid arthritis (RA)