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Researchers discover molecular trigger of inflammatory bowel disease

Cells lining the intestinal tract form a critical barrier, protecting our bodies from the billions of bacteria living in the gut. Breaches in this barrier are driven largely by a single signaling molecule called (), elevated amounts of which are associated with like Crohn’s disease and ulcerative colitis.

Fish IBD
Image of a zebrafish in which the entire intestine is highlighted in red and the expression of the TNF molecule is highlighted in green. Duke researchers have discovered that a gene called uhrf1 acts like a kind of molecular handbrake on TNF, keeping it from setting off the series of pro-inflammatory and immune signals that drive inflammatory bowel diseases.
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The research was supported by a National Institutes of Health New Innovator Award (DP2 3034656), a Bill & Melinda Gates Foundation Grand Challenges Exploration grant (OPP1108132), a Duke Multidisciplinary Fellowship in Pediatric Lung Disease (5T32HL098099-02), an F32 NRSA (DK098885-01A1), and a grant from the March of Dimes Foundation (5-FY12-93).

CITATION: “Epigenetic control of intestinal barrier function and inflammation in zebrafish,” Lindsay Marjoram, Ashley Alvers, M. Elizabeth Deerhake, Jennifer Bagwell, Jamie Mankiewicz, Jordan Cocchiaro, Rebecca W. Beerman, Jason Willer, Kaelyn Sumigray, Nicholas Katsanis, David M. Tobin, John F. Rawls, Mary Goll, Michel Bagnat. PNAS, Feb. 16, 2015. DOI: 10.1073/pnas.1424089112

Duke University