A Network Approach to Wound Healing

Arodź, Tomasz; Bonchev, Danail; Diegelmann, Robert F.

doi:10.1089/wound.2012.0386

Cited by 19 publications

(16 citation statements)

References 57 publications

(70 reference statements)

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“…Since the number of interactions between kinases may determine relative importance of a kinase to the network, we weighted our model using the number of interactions for each kinase in the network. 47 …”

Section: Methodsmentioning

confidence: 99%

Abnormalities of signal transduction networks in chronic schizophrenia

et al. 2017

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Schizophrenia is a serious neuropsychiatric disorder characterized by disruptions of brain cell metabolism, microstructure, and neurotransmission. All of these processes require coordination of multiple kinase-mediated signaling events. We hypothesize that imbalances in kinase activity propagate through an interconnected network of intracellular signaling with potential to simultaneously contribute to many or all of the observed deficits in schizophrenia. We established a workflow distinguishing schizophrenia-altered kinases in anterior cingulate cortex using a previously published kinome array data set. We compared schizophrenia-altered kinases to haloperidol-altered kinases, and identified systems, functions, and regulators predicted using pathway analyses. We used kinase inhibitors with the kinome array to test hypotheses about imbalance in signaling and conducted preliminary studies of kinase proteins, phosphoproteins, and activity for kinases of interest. We investigated schizophrenia-associated single nucleotide polymorphisms in one of these kinases, AKT, for genotype-dependent changes in AKT protein or activity. Kinome analyses identified new kinases as well as some previously implicated in schizophrenia. These results were not explained by chronic antipsychotic treatment. Kinases identified in our analyses aligned with cytoskeletal arrangement and molecular trafficking. Of the kinases we investigated further, AKT and (unexpectedly) JNK, showed the most dysregulation in the anterior cingulate cortex of schizophrenia subjects. Changes in kinase activity did not correspond to protein or phosphoprotein levels. We also show that AKT single nucleotide polymorphism rs1130214, previously associated with schizophrenia, influenced enzyme activity but not protein or phosphoprotein levels. Our data indicate subtle changes in kinase activity and regulation across an interlinked kinase network, suggesting signaling imbalances underlie the core symptoms of schizophrenia.

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Section: Methodsmentioning

confidence: 99%

Abnormalities of signal transduction networks in chronic schizophrenia

et al. 2017

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“…UBM has been used previously for complex wounds [14]. Previous reports have shown AlloDerm Ò can be used for covering giant omphaloceles and breast reconstruction [15].…”

Section: Discussionmentioning

confidence: 99%

Successful three stage repair of a large congenital abdominal region defect

Agrawal

Almond

Reyna

et al. 2015

Journal of Pediatric Surgery Case Reports

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“…In this study, we build on those results to investigate the nodes which are influential and essential in a network of biological processes involved in skin wound healing. Focusing on a network of biological processes is a new direction for wound healing studies that expands on our previous in-silico analyses of healing [30][31][32]. Our new approach might be regarded as a computationally oriented branch of the newly open field of network physiology [33][34][35] or, more generally, of the new 'network of networks' field [36].…”

Section: Introductionmentioning

confidence: 98%

Identifying influential nodes in a wound healing-related network of biological processes using mean first-passage time

Arodź

Bonchev

2015

New J. Phys.

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In this study we offer an approach to network physiology, which proceeds from transcriptomic data and uses gene ontology analysis to identify the biological processes most enriched in several critical time points of wound healing process (days 0, 3 and 7). The top-ranking differentially expressed genes for each process were used to build two networks: one with all proteins regulating the transcription of selected genes, and a second one involving the proteins from the signaling pathways that activate the transcription factors. The information from these networks is used to build a network of the most enriched processes with undirected links weighted proportionally to the count of shared genes between the pair of processes, and directed links weighted by the count of relationships connecting genes from one process to genes from the other. In analyzing the network thus built we used an approach based on random walks and accounting for the temporal aspects of the spread of a signal in the network (mean-first passage time, MFPT). The MFPT scores allowed identifying the top influential, as well as the top essential biological processes, which vary with the progress in the healing process. Thus, the most essential for day 0 was found to be the Wnt-receptor signaling pathway, well known for its crucial role in wound healing, while in day 3 this was the regulation of NF-kB cascade, essential for matrix remodeling in the wound healing process. The MFPT-based scores correctly reflected the pattern of the healing process dynamics to be highly concentrated around several processes between day 0 and day 3, and becoming more diffuse at day 7.

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A Network Approach to Wound Healing

Abstract: Network analysis has the potential to considerably contribute to the better understanding of the molecular mechanisms of wound healing and to the discovery of means to control and optimize that process.

Cited by 19 publications

References 57 publications

Abnormalities of signal transduction networks in chronic schizophrenia

Abnormalities of signal transduction networks in chronic schizophrenia

Successful three stage repair of a large congenital abdominal region defect

Identifying influential nodes in a wound healing-related network of biological processes using mean first-passage time

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