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This Week in Science: Mar 8, 2019

In Science Translational Medicine  this week, a group of US and Australian scientists reports the identification of a genetic mechanism underlying aggressive forms of inflammatory bowel disease (IBD). The researchers performed global transcriptome analysis on 1,800 intestinal biopsies from 14 independent cohorts and discovered that the coagulation gene pathway is one of the most enriched gene sets in patients with IBD. Notably, among the coagulation pathway genes, plasminogen activator inhibitor-1 (PAI-1) expression was highly enriched in active disease and in patients with IBD who did not respond to anti-TNF biologic therapy. PAI-1 was also found to be a key link between the epithelium and inflammation. In additional experiments, PAI-1 was found to promote inflammation by targeting another protein — called tPA — that is produced by the cells that line the intestine and protects against colon injury in mice. "This study identifies an immune-coagulation gene axis in IBD where elevated PAI-1 may contribute to more aggressive disease," the authors write. GenomeWeb has more on this, here.

Also in Science Translational Medicine, a Harvard Medical School-led team publishes a study uncovering an aging-associated molecular pathway that contributes to severe heart failure. The researchers focused on activin type II receptor (ActRII) ligands, which have been implicated in muscle wasting in aging and disease, and found higher levels of both activins, as well as a potential indicator of ActRII activity called FSTL3, in plasma samples from 50 heart failure patients. RNA sequencing revealed that activins boost the activity of a pathway that breaks down proteins in mammalian cardiomyocytes. Notably, blocking ActRII with either genetic deletion or clinical inhibitors reduced cardiac ActRII signaling and restored or preserved cardiac function in multiple models of heart failure.