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Transcription factor regulatory network for early lung immune response to tuberculosis in mice

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Numerous transcription factors (TFs) have been suggested to have a role in Mycobacterium tuberculosis infection; however, the TFs involved in the early immune response of lung cells remains to be fully elucidated. The present study aimed to identify TFs which may have a role in the early immune response to tuberculosis and the gene regulatory networks in which they are involved. Gene expression data obtained from microarray analysis of the early lung immune response to tuberculosis (Gene Expression Omnibus; accession no. GSE23014) was integrated with data for TF binding sites and proteinprotein interactions in order to construct a TF regulatory network. The role of TFs in protein complexes, active modules, topology of the network and regulation of immune processes were investigated. The results demonstrated that the constructed gene regulatory network harbored 1,270 differentially expressed (DE) genes with 4,070 regulatory and proteinprotein interactions. In addition, it was revealed that 17 DE TFs were involved in the positive regulation of numerous immunological and biological processes, including T cell activation, T cell proliferation and tuberculosisassociated gene expression, in the constructed regulatory network. Signal transducer and activator of transcription 4, interferon regulatory factor 8, spleen focus-forming virus proviral integration 1, enhancer of zeste homolog 2 and kruppellike factor 4 were predicted to be the primary TFs regulating the DE genes during early lung infection by M. tuberculosis, as determined through various analyses of the gene regulatory network. In conclusion, the present study identified novel TFs involved in the early response to M. tuberculosis infection, which may enhance current understanding of the molecular mechanism underlying tuberculosis infection and introduced potential targets for novel tuberculosis therapies.
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Document Type: Research Article

Affiliations: 1: Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran 14178-63171, Iran 2: Department of Molecular Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran 14178-63171, Iran 3: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 6714967346, Iran

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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