Abstract

Prolyl hydroxylases (PHD1–3) hydroxylate hypoxia inducible factor α (HIFα), leading to HIFα ubiquitination and degradation. Recent studies indicated that administration of generic inhibitors of PHDs improved mice colitis, suggesting that suppression of PHD activity by these inhibitors may be a potential strategy for the treatment of inflammatory bowel diseases. However, the exact role of each member of PHD family in homeostasis of intestinal epithelium remains elusive. The aim of this work is to study the possible role of PHD2 by using mice with genetic ablation of Phd2 in intestinal epithelial cells (IECs). We found that deletion of PHD2 in IECs did not lead to spontaneous enteritis or colitis in mice. Deletion of PHD2 in IECs did not confer upon mice higher susceptibility to dextran sodium sulfate-induced colitis. Furthermore, in a colitis-associated colon cancer model, the PHD2-conditional knockout mice had similar susceptibility to azoxymethane (AOM)-induced colonic tumorigenesis as control mice did. Our results suggest that PHD2 is dispensable for maintenance of intestinal epithelium homeostasis in mice.