Expression of REG family genes in human inflammatory bowel diseases and its regulation.
Expression of REG family genes in human inflammatory bowel diseases and its regulation.
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DOI：
10.1016/j.bbrep.2017.10.003
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发表时间：
2017-12-01
影响因子：
2.7
通讯作者：
Takasawa, Shin
中科院分区：
文献类型：
--
作者：
Tsuchida, Chikatsugu;Sakuramoto-Tsuchida, Sumiyo;Takasawa, Shin
The 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 REG family genes in IBD is still unclear. Here, we analyzed expression of all REG family genes (REG Ialpha, REG Ibeta, REG III, HIP/PAP, and REG IV) in biopsy specimens of UC and CD by real-time RT-PCR. REG Ialpha, REG Ibeta, and REG IV genes were overexpressed in CD samples. REG IV gene was also overexpressed in UC samples. We further analyzed the expression mechanisms of REG Ialpha, REG Ibeta, and REG IV genes in human colon cells. The expression of REG Ialpha was significantly induced by IL-6 or IL-22, and REG Ibeta was induced by IL-22. Deletion analyses revealed that three regions (- 220 to - 211, - 179 to - 156, and - 146 to - 130) in REG Ialpha and the region (- 274 to- 260) in REG Ibeta 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 REG Ialpha, and HLTF/FOXN2F in REG Ibeta, respectively. The introduction of siRNAs for MZF1, RTEF1/TEAD4, STAT3, and HLTF/FOXN2F abolished the transcription of REG Ialpha and REG Ibeta. The gene activation mechanisms of REG Ialpha/REG Ibeta may play a role in colon mucosal regeneration in IBD.
