Project description:Arnica m. effects were associated with a purported anti-inflammatory and tissue healing actions after trauma, bruises, or tissue injuries, but its cellular and molecular mechanisms are largely unknown. Here Arnica m. dilutions were tested using an in vitro model of macrophages polarized towards a “wound-healing” phenotype. The monocyte-macrophage human THP-1 cell line was cultured and differentiated with phorbol-myristate acetate and Interleukin-4, then exposed for 24 h to Arnica m. centesimal (c) dilutions 2c, 3c, 5c,9c, 15c or Control. None of these treatments affected cell viability. A total of 20 genes were differentially expressed comparing cells treated with Arnica m. 2c with those treated with Control only. Of these, 7 genes were up-regulated and 13 were down-regulated. Functional gene enrichment analysis showed that the most significantly upregulated function concerned 4 genes with a conserved site of EGF-like region (p<0.001) and three genes of proteinaceous extracellular matrix, including heparin sulphate proteoglycan 2 (HSPG2), fibrillin 2 (FBN2), and fibronectin (FN1) (p <0.01). Protein assay in supernatants confirmed a statistically significant increase of fibronectin production in Arnica m. 2c treated cells (p<0.05). Pooled extracts of cells treated with increasing dilutions of Arnica m. (3c, 5c, 15c) showed up-regulation of the same group of genes although with lower effect size. The down-regulated transcripts derive from mitochondrial genes coding for some components of electron transport chain. These findings provide new insights into the action of Arnica m. in tissue healing and repair, identifying increased fibronectin production by macrophages as a major therapeutic target.
Project description:Arnica m. effects were associated with a purported anti-inflammatory and tissue healing actions after trauma, bruises, or tissue injuries, but its cellular and molecular mechanisms are largely unknown. Here Arnica m. dilutions were tested using an in vitro model of macrophages polarized towards a “wound-healing” phenotype. The monocyte-macrophage human THP-1 cell line was cultured and differentiated with phorbol-myristate acetate and Interleukin-4, then exposed for 24 h to Arnica m. centesimal (c) dilutions 2c, 3c, 5c,9c, 15c or Control. None of these treatments affected cell viability. A total of 20 genes were differentially expressed comparing cells treated with Arnica m. 2c with those treated with Control only. Of these, 7 genes were up-regulated and 13 were down-regulated. Functional gene enrichment analysis showed that the most significantly upregulated function concerned 4 genes with a conserved site of EGF-like region (p<0.001) and three genes of proteinaceous extracellular matrix, including heparin sulphate proteoglycan 2 (HSPG2), fibrillin 2 (FBN2), and fibronectin (FN1) (p <0.01). Protein assay in supernatants confirmed a statistically significant increase of fibronectin production in Arnica m. 2c treated cells (p<0.05). Pooled extracts of cells treated with increasing dilutions of Arnica m. (3c, 5c, 15c) showed up-regulation of the same group of genes although with lower effect size. The down-regulated transcripts derive from mitochondrial genes coding for some components of electron transport chain. These findings provide new insights into the action of Arnica m. in tissue healing and repair, identifying increased fibronectin production by macrophages as a major therapeutic target.
Project description:Co-expression networks and gene regulatory networks (GRNs) are emerging as important tools for predicting the functional roles of individual genes at a system-wide scale. To enable network reconstructions we built a large-scale gene expression atlas comprised of 62,547 mRNAs, 17,862 non-modified proteins, and 6,227 phosphoproteins harboring 31,595 phosphorylation sites quantified across maize development. There was little edge conservation in co-expression and GRNs reconstructed using transcriptome versus proteome data yet networks from either data type were enriched in ontological categories and effective in predicting known regulatory relationships. This integrated gene expression atlas provides a valuable community resource. The networks should facilitate plant biology research and they provide a conceptual framework for future systems biology studies highlighting the importance of studying gene regulation at several levels.
Project description:Co-expression networks and gene regulatory networks (GRNs) are emerging as important tools for predicting the functional roles of individual genes at a system-wide scale. To enable network reconstructions we built a large-scale gene expression atlas comprised of 62,547 mRNAs, 17,862 non-modified proteins, and 6,227 phosphoproteins harboring 31,595 phosphorylation sites quantified across maize development. There was little edge conservation in co-expression and GRNs reconstructed using transcriptome versus proteome data yet networks from either data type were enriched in ontological categories and effective in predicting known regulatory relationships. This integrated gene expression atlas provides a valuable community resource. The networks should facilitate plant biology research and they provide a conceptual framework for future systems biology studies highlighting the importance of studying gene regulation at several levels.
