Significant Deregulated Pathways in Diabetes Type II Complications Identified through Expression Based Network Biology

  • Sanchaita Ukil
  • Meenakshee Sinha
  • Lavneesh Varshney
  • Shipra Agrawal
Part of the Communications in Computer and Information Science book series (CCIS, volume 40)

Abstract

Type 2 Diabetes is a complex multifactorial disease, which alters several signaling cascades giving rise to serious complications. It is one of the major risk factors for cardiovascular diseases. The present research work describes an integrated functional network biology approach to identify pathways that get transcriptionally altered and lead to complex complications thereby amplifying the phenotypic effect of the impaired disease state. We have identified two sub-network modules, which could be activated under abnormal circumstances in diabetes. Present work describes key proteins such as P85A and SRC serving as important nodes to mediate alternate signaling routes during diseased condition. P85A has been shown to be an important link between stress responsive MAPK and CVD markers involved in fibrosis. MAPK8 has been shown to interact with P85A and further activate CTGF through VEGF signaling. We have traced a novel and unique route correlating inflammation and fibrosis by considering P85A as a key mediator of signals. The next sub-network module shows SRC as a junction for various signaling processes, which results in interaction between NF-kB and beta catenin to cause cell death. The powerful interaction between these important genes in response to transcriptionally altered lipid metabolism and impaired inflammatory response via SRC causes apoptosis of cells. The crosstalk between inflammation, lipid homeostasis and stress, and their serious effects downstream have been explained in the present analyses.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Sanchaita Ukil
    • 1
  • Meenakshee Sinha
    • 1
  • Lavneesh Varshney
    • 1
    • 2
  • Shipra Agrawal
    • 1
  1. 1.Institute of Bioinformatics and Applied BiotechnologyIndia
  2. 2.International Technology Park Bangalore (ITPB)BioCOS Life Sciences Pvt. Limited, G-05, Tech Park MallBangaloreIndia

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