The Role Of Nur77 In Inflammatory Bowel Disease

Orphan nuclear receptor Nur77(NR4A1、TR3 or NGFI-B), a member of the nuclear receptor superfamily, plays a critical role in the physiological and pathological process.Nur77 is known as one of the immediate-early genes, and is rapidly induced by various inflammatory cytokines, including lipopolysaccharide(LPS), tumour necrosis factor-α(TNFα), interferon-γ(IFN-γ) and Low-density lipoprotein(LDL) oxidation type(ox-LDL). Recently, Accumulating studies have shown that Nur77 is implicated in atherosclerosis, metabolic diseases and tumor. However, the role of Nur77 in inflammatory bowel disease remains to be elusive. Here, using the mouse model for inflammatory bowel disease and the clinical samples of inflammatory bowel disease, we try to determine the role of Nur77 in inflammatory bowel disease. Our results showed that the Nur77 knockout mice are more prone to develop spontaneous inflammatory diseases compared with the wild type mice. In the DSS-induced colitis model, we found the severe inflammation and crypt damage in colon tissue of Nur77 knockout mice during the DSS treatment and recovery periods. In line with this, the concentration of IL-6 was significantly higher in Nur77 knockout mice. Importantly, Nur77 expression was lower in colonic mucosal tissues of patients with Crohn’s disease(CD) and Ulcerative colitis(UC). Collectively, we here identify Nur77 as an important negative regulator in inflammatory bowel disease.