Epithelial hypoxia-inducible factor-1 protects against experimental colitis.

2004 DEC 29 - (NewsRx.com & NewsRx.net) -- Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis.

According to recent research from the United States, "Mucosal epithelial cells are uniquely equipped to maintain barrier function even under adverse conditions. Previous studies have implicated hypoxia in mucosal tissue damage resulting from both acute and chronic inflammation. Given the importance of the transcriptional regulator hypoxia-inducible factor-1 (HIF-1) for adaptive hypoxia responses, we hypothesized that HIF-1 may serve as a barrier-protective element during mucosal inflammation. Initial studies of hapten-based murine colitis revealed extensive mucosal hypoxia and concomitant HIF-1 activation during colitis."

"To study this in more detail, we generated two mouse lines with intestinal epithelium-targeted expression of either mutant Hif1a (inability to form HIF-1) or mutant von Hippel-Lindau gene (Vblb; constitutively active HIF-1)," said Jorn Karhausen at Brigham and Women's Hospital and collaborators in the U.S. "Studies of colitis in these mice revealed that decreased HIF-1 expression correlated with more severe clinical symptoms (mortality, weight loss, colon length), while increased HIF levels were protective in these parameters."

"Furthermore, colons with constitutive activation of HIF displayed increased ...