title: Role of RNA-binding protein tristetraprolin in tumor necrosis factor-α mediated gene expression.
abstract: Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis of inflammatory diseases. Excessive TNF-α expression induces tristetraprolin (TTP), an RNA-binding protein that regulates mRNA degradation, which in turn downregulates TNF and its downstream genes, thus resulting in anti-inflammatory effects. In order to better understand the TNF-α mediated molecular pathways in inflammatory diseases, embryonic fibroblast (MEF) cell lines derived from TTP-deficient (KO) or wild type (WT) mice were treated with TNF-α and gene expression differences between two cell lines were compared by a microarray essay of 9224 genes. We found that TTP-KO cells had higher expression levels of pro-inflammatory genes than TTP-WT cells, and inflammatory genes were differentially regulated by TNF-α between TTP-KO and TTP-WT cells. Through a study of 2-dimentional gene set matrix analysis, we also found the genes upregulated by TNF-α in TTP KO cells were correlated with the pathologic phenotypes in inflammation, joint, or bone diseases. Our study provided a detailed genetic roadmap for further understanding the regulatory effect of TTP in inflammatory pathways related to human diseases.
authors.affiliation: Urology Department, Minhang District Central Hospital, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Ziran
authors.initials: Z
authors.lastname: Wei
authors.forename: Weimin
authors.initials: W
authors.lastname: Wang
authors.forename: Ronlin
authors.initials: R
authors.lastname: Yan
authors.forename: Xudong
authors.initials: X
authors.lastname: Xu
authors.forename: Qingping
authors.initials: Q
authors.lastname: Cai
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051816:Tristetraprolin / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: D016601:RNA-Binding Proteins; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha; C497553:Zfp36 protein, mouse