On the other hand, Shah et al. (2008) have shown that constitutive upregulation of HIF in epithelial cells by targeted disruption of Vhl in villin-positive epithelial cells leads to exacerbated colitis in mice through increased expression of macrophage migration inhibitory factor, an HIF-target gene in a dextran sodium sulfate (DSS)-induced colitis model, in which immune responses secondary to disruption of the epithelial barrier prevail (Chassaing et al., 2014). This evidence concerns the gene VHL and colitis.