Research ArticleInflammation

Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis

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Science Signaling  27 Feb 2018:
Vol. 11, Issue 519, eaan3580
DOI: 10.1126/scisignal.aan3580

Tracking inflammation in disease

Crohn’s disease and ulcerative colitis are forms of inflammatory bowel disease (IBD), which have limited therapeutic options. Thus, a better understanding of the molecular mechanisms underlying IBD is needed to develop new treatment strategies. Lyons et al. combined RNA microarray, total protein mass spectrometry, and phosphoprotein mass spectrometry analyses of tissues isolated from a mouse model of colitis. Integration of these data sets enabled tracking from gene expression to protein phosphorylation in individual animals over time. Computational analysis of the data identified discrepancies between transcriptomic and proteomic measurements and predicted that the kinase Pak1 mediated colonic inflammation. Treatment of mice with a pharmacological inhibitor of Pak1 ameliorated disease, highlighting the importance of proteomic measurement to the understanding of disease pathogenesis.

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