PMC

(A) Gene network analysis in the bone marrow of active versus inactive patients with SLE revealed 30 central nodes, and (B) 9 gene sub-networks that illustrate major functions of these pathways. (C) The most significant network consists of proteins that are up-regulated in active patients. See legend for more details on gene network analysis and description.

(A) Western blot analysis in isolated spleen B cells from lupus NZB/NZW F1 mice revealed activation of several kinases identified in gene network analysis. ERK1/2, SAPK/JNK, and p38 MAPK kinases were phosphorylated while their total protein levels were not altered in NZB/NZW F1 compared to control C57Bl/6 (B6) mice. (B) Activation of AKT signaling pathway in NZB/NZW F1 mice. Quantitative real-time PCR (C) and western blot (D) analysis in isolated spleen B cells demonstrated downregulation of FOXO3 and VDR, and upregulation of STAT3, pSTAT3, ITGB2, and HSPB1 in NZB/NZW F1 compared to B6 mice.

(A) A gene network of 19 central nodes was constructed by using the differentially expressed genes in the bone marrow of SLE patients and controls, as described in . Deletion of any of these nodes pertubates or destroys the gene network. Genes are colored according to gene expression value; red gene symbols indicate up-regulation and green gene symbols indicate down-regulation. Nodes are displayed using various shapes that represent the functional class of the gene product. Edges with dashed lines show indirect interaction, while a continuous line represents direct interactions (see explanatory inset). (B) Four gene sub-networks are related to nucleic and amino acid metabolism, cell growth and protein synthesis. A dataset containing the differentially expressed genes, called the focus molecules, between SLE and controls was overlaid onto a global molecular network developed from information contained in the Ingenuity Pathways Knowledge Base. Networks of these focus molecules were then algorithmically generated based on their connectivity. The composite score of the networks represents the negative log of the p-value for the likelihood that network molecules would be found together by chance. Accordingly, a higher score indicates greater statistical significance that molecules depicted in the network are interconnected. (C) The most significant gene network is involved in cellular growth.