Research ArticleColitis

PAI-1 augments mucosal damage in colitis

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Science Translational Medicine  06 Mar 2019:
Vol. 11, Issue 482, eaat0852
DOI: 10.1126/scitranslmed.aat0852

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A punch to the gut by PAI-1

Only a fraction of patients with inflammatory bowel disease (IBD) respond to therapy. To look for pathways that could distinguish difficult-to-treat patients, Kaiko et al. examined transcriptomic datasets from cohorts of patients with IBD. They found that genes normally associated with the coagulation pathway were increased in those with severe disease. These genes intersected clusters of inflammatory myeloid cells and epithelial cells, two cell types that closely interact. One player of the coagulation pathway, PAI-1, exacerbated mucosal damage in mouse colitis models. Pharmacologic inhibition of PAI-1 alleviated symptoms in these models. Their results highlight this previously unappreciated axis in mucosal wounding in IBD and could open up new avenues of treatment for patients refractory to other biologics.

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