XXXX sensing in @entity32 .

@entity9474 @entity32 @entity455 @entity28269 @entity19 @entity26 @entity29 @entity1960 @entity519 @entity1965 @entity10783 @entity22168
@entity519 is a hallmark of chronically inflamed tissue. @entity519 develops from @entity455 and increased @entity26 consumption by infiltrating leukocytes. With respect to @entity29 ( @entity29 ), @entity519 is likely to be of particular importance: Impairment of the intestinal barrier during @entity29 allows @entity519 from the lumen of the gut to spread to formerly normoxic tissue. In addition, disturbed perfusion of inflamed tissue and a higher @entity26 demand of infiltrating immune cells lead to low @entity26 levels in inflamed mucosal tissue. Here, cells become @entity519 and must now adapt to this condition. The @entity519 inducible factor (HIF)-1 complex is a key transcription factor for cellular adaption to low @entity26 tension. HIF-1 is a heterodimer formed by two subunits: HIF-a (either @entity1965 or @entity22168 ) and @entity28269 . Under normoxic conditions, hydroxylation of the HIF-a subunit by specific @entity26 -dependent @entity10783 hydroxylases (PHDs) leads to ubiquitin proteasome-dependent degradation. Under @entity519 conditions, however, @entity9474 activity is inhibited; thus, HIF-a can translocate into the nucleus, dimerize with @entity28269 , and bind to @entity519 -responsive elements of HIF-1 target genes. So far, most studies have addressed the function of @entity1965 in intestinal epithelial cells and the effect of HIF stabilization by @entity9474 inhibitors in @entity19 models of @entity1960 . Furthermore, the role of @entity1965 in immune cells becomes more and more important as T cells or dendritic cells for which HIF-1 is of critical importance are highly involved in the pathogenesis of @entity29 . This review will summarize the function of @entity1965 and the therapeutic prospects for targeting the HIF pathway in @entity32 .
