We are analyzing https://link.springer.com/article/10.1186/1755-8794-2-24.

Title:
Network analysis of human glaucomatous optic nerve head astrocytes | BMC Medical Genomics
Description:
Background Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive. Methods To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs). Results Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by genetic analysis can be functionally interconnected into one epistatic network via experimentally-validated interactions. Finally, we built and analyzed an integrative disease pathology network from a combined set of genes revealed in genetic studies, genes differentially expressed in glaucoma and closely connected genes/proteins in the interactome. Conclusion Our results suggest several key biological network modules that are involved in regulating neurotoxicity of reactive astrocytes in glaucoma, and comprise potential targets for cell-based therapy.
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28 years and 1 months (reg. 1997-05-29).

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Keywords {🔍}

data, genes, network, pubmed, google, scholar, analysis, cas, glaucoma, activation, gene, expression, table, glaucomatous, supplement, networks, figure, astrocytes, file, additional, human, set, optic, onhas, normal, nerve, proteins, nodes, complement, cell, pathways, size, signaling, transcription, protein, factors, combined, experimental, nfκb, number, major, activated, list, receptor, disease, processes, response, reactive, metacore, downregulated,

Topics {✒️}

neuroactive steroid 5alpha-androstane-3alpha primary open-angle glaucoma ap-1/c-fos/c-jun complex open access article ap-1/c-fos/c-jun [5 nf-κb-controlled transcriptional program c-jun-ap-1 protective pathway transcription factors ap-1/c-fos protein-coupled receptor agonists mid-america eye bank transcription factor c-jun functional proximity search shotgun ms/ms analysis heat-shock protein hsp70 elevated intraocular pressure full size image literature-derived g-set data parathyroid hormone-related protein enzyme 3α-hydroxysteroid dehydrogenase age-related macular degeneration virus-infected brain astrocytes nmda-induced retinal neurotoxicity optic nerve head human anti-clusterin antibodies real time rt-pcr affected pro-inflammatory pathways ap-1 subunits c-jun high-content experimental data normal-appearing white matter ap-1 subunit c-fos high-content experimental datasets full access p65/c-rel subunits nuclear factor-kappab revealed highly-coordinated activation regulated modules c-myb vdr-mediated signaling pathway central nervous system g-set gene content nf-kappabetap50-deficient mice article download pdf pre-publication history clusterin included c-fos hypoxic-ischemic brain injury integrated software platform elevated hydrostatic pressure regulated affi/hugo ids anti-mouse igg nf-kb forms primary antibodies omitted

Schema {🗺️}

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         description:Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive. To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs). Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by genetic analysis can be functionally interconnected into one epistatic network via experimentally-validated interactions. Finally, we built and analyzed an integrative disease pathology network from a combined set of genes revealed in genetic studies, genes differentially expressed in glaucoma and closely connected genes/proteins in the interactome. Our results suggest several key biological network modules that are involved in regulating neurotoxicity of reactive astrocytes in glaucoma, and comprise potential targets for cell-based therapy.
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      headline:Network analysis of human glaucomatous optic nerve head astrocytes
      description:Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive. To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs). Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by genetic analysis can be functionally interconnected into one epistatic network via experimentally-validated interactions. Finally, we built and analyzed an integrative disease pathology network from a combined set of genes revealed in genetic studies, genes differentially expressed in glaucoma and closely connected genes/proteins in the interactome. Our results suggest several key biological network modules that are involved in regulating neurotoxicity of reactive astrocytes in glaucoma, and comprise potential targets for cell-based therapy.
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         Androgen Receptor
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         Input List
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         Microarrays
         Gene Expression
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      name:GeneGo Inc, MI, USA
      name:GeneGo Inc, MI, USA
      name:Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
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      name:Department of Molecular Biology and Biochemistry, University of Miami Miller School of Medicine, Miami, USA
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      name:Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, USA

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