Expression of family genes in human inflammatory bowel diseases and its regulation.

The pathophysiology of inflammatory bowel disease (IBD) reflects a balance between mucosal injury and reparative mechanisms. Some regenerating gene () family members have been reported to be expressed in Crohn's disease (CD) and ulcerative colitis (UC) and to be involved as proliferative mucosal factors in IBD. However, expression of all family genes in IBD is still unclear. Here, we analyzed expression of all family genes (, , , , and ) in biopsy specimens of UC and CD by real-time RT-PCR. , , and genes were overexpressed in CD samples. gene was also overexpressed in UC samples. We further analyzed the expression mechanisms of , , and genes in human colon cells. The expression of was significantly induced by IL-6 or IL-22, and was induced by IL-22. Deletion analyses revealed that three regions (- 220 to - 211, - 179 to - 156, and - 146 to - 130) in and the region (- 274 to- 260) in promoter were responsible for the activation by IL-22/IL-6. The promoters contain consensus transcription factor binding sequences for MZF1, RTEF1/TEAD4, and STAT3 in , and HLTF/FOXN2F in , respectively. The introduction of siRNAs for MZF1, RTEF1/TEAD4, STAT3, and HLTF/FOXN2F abolished the transcription of and . The gene activation mechanisms of may play a role in colon mucosal regeneration in IBD.