Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Connective tissue growth factor (CTGF/CCN2) is a matricellular protein induced by transforming growth factor (TGF)-beta and intimately involved with tissue repair and overexpressed in various fibrotic conditions. We previously showed that keratinocytes in vitro downregulate TGF-beta-induced expression of CTGF in fibroblasts by an interleukin (IL)-1 alpha-dependent mechanism. Here, we investigated further the mechanisms of this downregulation by both IL-1alpha and beta. Human dermal fibroblasts and NIH 3T3 cells were treated with IL-1alpha or beta in presence or absence of TGF-beta1. IL-1 suppressed basal and TGF-beta-induced CTGF mRNA and protein expression. IL-1alpha and beta inhibited TGF-beta-stimulated CTGF promoter activity, and the activity of a synthetic minimal promoter containing Smad 3-binding CAGA elements. Furthermore, IL-1alpha and beta inhibited TGF-beta-stimulated Smad 3 phosphorylation, possibly linked to an observed increase in Smad 7 mRNA expression. In addition, RNA interference suggested that TGF-beta activated kinase1 (TAK1) is necessary for IL-1 inhibition of TGF-beta-stimulated CTGF expression. These results add to the understanding of how the expression of CTGF in human dermal fibroblasts is regulated, which in turn may have implications for the pathogenesis of fibrotic conditions involving the skin.
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PMID:Inhibition of connective tissue growth factor/CCN2 expression in human dermal fibroblasts by interleukin-1alpha and beta. 2054 97

Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) is a complex disease, leading to the damage of multiple systems. The pathogen that triggers this sophisticated disease is still unknown. The aim of this study was to identify gene signatures during IVIG-resistant KD and uncover their potential mechanisms. The gene expression profiles of GSE18606 were downloaded from the GEO database. The GSE18606 dataset contained eight IVIG-resistant KD samples and nine healthy age-appropriate controls. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. In total, 73 DEGs were identified in IVIG-resistant KD, including 58 upregulated genes and 15 downregulated genes. GO analysis results showed that DEGs were significantly enriched in biological processes of neutrophil degranulation, neutrophil mediated immunity, and neutrophil activation involved in immune response. Among them, 10 hub genes (S100A8, S100A9, S100A12, HGF, LCN2, LY96, CTGF, MMP8, IRAK3, and SLPI) with a high degree of connectivity were selected. The present study indicated that the identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of IVIG-resistant KD, and might be used as molecular targets and diagnostic biomarkers for the treatment of IVIG-resistant KD.
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PMID:Identification of Potential Core Genes in Immunoglobulin-Resistant Kawasaki Disease Using Bioinformatics Analysis. 3242 87