Expression of human REG family genes in inflammatory bowel disease and their molecular mechanism

AbstractThe pathophysiology of inflammatory bowel disease (IBD) reflects a balance between mucosal injury and reparative mechanisms. Some regenerating gene (Reg) 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 theREG family genes in IBD is still unclear. Here, we analyzed expression of all theREG family genes (REGI α,REGI β,REG III,HIP/PAP, andREG IV) in biopsy specimens of UC and CD by real-time RT-PCR.REG I α,REG I β, andREG IV genes were overexpressed in CD samples.REG IV gene was also overexpressed in UC samples. We further analyzed the expression mechanisms ofREG I α,REG I β, andREG IV genes in LS-174T and HT-29 human colonic epithelial cells. The expression ofREG I α was significantly induced by IL-6 or IL-22, andREG I β was induced by IL-22. Deletion analyses revealed that three regions ( − 220~− 211, − 179~− 156, and − 146~− 130) inREG I α and the region ( − 274~− 260) inREG I β 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 inREG I α, and HLTF/FOXN2F inREG I β, respectively. The introduction of siRNA for MZF1, RTEF1/TEAD4, STAT3, and HLTF/FOXN2F abolished the transcription ofREG I α andREG I β. The gene activation mechanisms ofREG I α/REG Iβ may play a role in col...
Source: Immunologic Research - Category: Allergy & Immunology Source Type: research