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Gene regulatory network reveals oxidative stress as the underlying molecular mechanism of type 2 diabetes and hypertension.

Jesmin J, Rashid MS, Jamil H, Hontecillas R, Bassaganya-Riera J - BMC Med Genomics (2010)

Bottom Line: The present work, applied a systems biology approach to develop gene interaction network models, comprised of high throughput genomic and PPI data for T2D.Based on the investigations around the 'hubs' that provided more meaningful insights about the cross-talk within gene-disease networks in terms of disease phenotype association with oxidative stress and inflammation, a hypothetical co-regulation disease mechanism model been proposed.The findings provide a novel comprehensive approach for understanding the pathogenesis of various co-associated chronic inflammatory diseases by combining the power of pathway analysis with gene regulatory network evaluation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetic Engineering and Biotechnology, University of Dhaka, Bangladesh. jesmin@univdhaka.edu

ABSTRACT

Background: The prevalence of diabetes is increasing worldwide. It has been long known that increased rates of inflammatory diseases, such as obesity (OBS), hypertension (HT) and cardiovascular diseases (CVD) are highly associated with type 2 diabetes (T2D). T2D and/or OBS can develop independently, due to genetic, behavioral or lifestyle-related variables but both lead to oxidative stress generation. The underlying mechanisms by which theses complications arise and manifest together remain poorly understood. Protein-protein interactions regulate nearly every living process. Availability of high-throughput genomic data has enabled unprecedented views of gene and protein co-expression, co-regulations and interactions in cellular systems.

Methods: The present work, applied a systems biology approach to develop gene interaction network models, comprised of high throughput genomic and PPI data for T2D. The genes differentially regulated through T2D were 'mined' and their 'wirings' were studied to get a more complete understanding of the overall gene network topology and their role in disease progression.

Results: By analyzing the genes related to T2D, HT and OBS, a highly regulated gene-disease integrated network model has been developed that provides useful functional linkages among groups of genes and thus addressing how different inflammatory diseases are connected and propagated at genetic level. Based on the investigations around the 'hubs' that provided more meaningful insights about the cross-talk within gene-disease networks in terms of disease phenotype association with oxidative stress and inflammation, a hypothetical co-regulation disease mechanism model been proposed. The results from this study revealed that the oxidative stress mediated regulation cascade is the common mechanistic link among the pathogenesis of T2D, HT and other inflammatory diseases such as OBS.

Conclusion: The findings provide a novel comprehensive approach for understanding the pathogenesis of various co-associated chronic inflammatory diseases by combining the power of pathway analysis with gene regulatory network evaluation.

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Related in: MedlinePlus

Proposed hypothetical model of T2D mechanism.
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Figure 9: Proposed hypothetical model of T2D mechanism.

Mentions: Based on an elaborate study of the key 'hubs' regulations, their association, along with detailed literature reviewing - in this work we put the puzzle pieces together and proposed a hypothetical mechanism for co-regulation of various inflammatory diseases like T2D, HT and OBS (Figure 9). From the generated regulatory networks around key 'hub' genes it is very much visible that via EP300 the main pathways like insulin signaling, PPAR signaling, calcium signaling, adipocytokine signaling, Jak-STAT signaling pathway, MAPK signaling pathways that are well recognised in association with disease like T2D, OBS and HT. Interestingly, the analyses of the regulatory cascades showed that the genes involved in main disease pathways are all connected and regulated via the genes involved in Wnt-signaling and p53 signaling pathways.


Gene regulatory network reveals oxidative stress as the underlying molecular mechanism of type 2 diabetes and hypertension.

Jesmin J, Rashid MS, Jamil H, Hontecillas R, Bassaganya-Riera J - BMC Med Genomics (2010)

Proposed hypothetical model of T2D mechanism.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2965702&req=5

Figure 9: Proposed hypothetical model of T2D mechanism.
Mentions: Based on an elaborate study of the key 'hubs' regulations, their association, along with detailed literature reviewing - in this work we put the puzzle pieces together and proposed a hypothetical mechanism for co-regulation of various inflammatory diseases like T2D, HT and OBS (Figure 9). From the generated regulatory networks around key 'hub' genes it is very much visible that via EP300 the main pathways like insulin signaling, PPAR signaling, calcium signaling, adipocytokine signaling, Jak-STAT signaling pathway, MAPK signaling pathways that are well recognised in association with disease like T2D, OBS and HT. Interestingly, the analyses of the regulatory cascades showed that the genes involved in main disease pathways are all connected and regulated via the genes involved in Wnt-signaling and p53 signaling pathways.

Bottom Line: The present work, applied a systems biology approach to develop gene interaction network models, comprised of high throughput genomic and PPI data for T2D.Based on the investigations around the 'hubs' that provided more meaningful insights about the cross-talk within gene-disease networks in terms of disease phenotype association with oxidative stress and inflammation, a hypothetical co-regulation disease mechanism model been proposed.The findings provide a novel comprehensive approach for understanding the pathogenesis of various co-associated chronic inflammatory diseases by combining the power of pathway analysis with gene regulatory network evaluation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetic Engineering and Biotechnology, University of Dhaka, Bangladesh. jesmin@univdhaka.edu

ABSTRACT

Background: The prevalence of diabetes is increasing worldwide. It has been long known that increased rates of inflammatory diseases, such as obesity (OBS), hypertension (HT) and cardiovascular diseases (CVD) are highly associated with type 2 diabetes (T2D). T2D and/or OBS can develop independently, due to genetic, behavioral or lifestyle-related variables but both lead to oxidative stress generation. The underlying mechanisms by which theses complications arise and manifest together remain poorly understood. Protein-protein interactions regulate nearly every living process. Availability of high-throughput genomic data has enabled unprecedented views of gene and protein co-expression, co-regulations and interactions in cellular systems.

Methods: The present work, applied a systems biology approach to develop gene interaction network models, comprised of high throughput genomic and PPI data for T2D. The genes differentially regulated through T2D were 'mined' and their 'wirings' were studied to get a more complete understanding of the overall gene network topology and their role in disease progression.

Results: By analyzing the genes related to T2D, HT and OBS, a highly regulated gene-disease integrated network model has been developed that provides useful functional linkages among groups of genes and thus addressing how different inflammatory diseases are connected and propagated at genetic level. Based on the investigations around the 'hubs' that provided more meaningful insights about the cross-talk within gene-disease networks in terms of disease phenotype association with oxidative stress and inflammation, a hypothetical co-regulation disease mechanism model been proposed. The results from this study revealed that the oxidative stress mediated regulation cascade is the common mechanistic link among the pathogenesis of T2D, HT and other inflammatory diseases such as OBS.

Conclusion: The findings provide a novel comprehensive approach for understanding the pathogenesis of various co-associated chronic inflammatory diseases by combining the power of pathway analysis with gene regulatory network evaluation.

Show MeSH
Related in: MedlinePlus