TY - JOUR
T1 - Expression of REG family genes in human inflammatory bowel diseases and its regulation
AU - Tsuchida, Chikatsugu
AU - Sakuramoto-Tsuchida, Sumiyo
AU - Taked, Maiko
AU - Itaya-Hironaka, Asako
AU - Yamauchi, Akiyo
AU - Misu, Masayasu
AU - Shobatake, Ryogo
AU - Uchiyama, Tomoko
AU - Makino, Mai
AU - Pujol-Autonell, Irma
AU - Vives-Pi, Marta
AU - Ohbayashi, Chiho
AU - Takasawa, Shin
PY - 2017/12/1
Y1 - 2017/12/1
N2 - © 2017 The Authors 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 Iα REG Iβ REG III, HIP/PAP, and REG IV) in biopsy specimens of UC and CD by real-time RT-PCR. REG Iα REG Iβ 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 Iα REG Iβ and REG IV genes in human colon cells. The expression of REG Iα was significantly induced by IL-6 or IL-22, and REG Iβ was induced by IL-22. Deletion analyses revealed that three regions (− 220 to − 211, − 179 to − 156, and − 146 to − 130) in REG Iα and the region (− 274 to− 260) in REG Iβ 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 Iα and HLTF/FOXN2F in REG Iβ respectively. The introduction of siRNAs for MZF1, RTEF1/TEAD4, STAT3, and HLTF/FOXN2F abolished the transcription of REG Iα and REG Iβ. The gene activation mechanisms of REG Iα/REG Iβ may play a role in colon mucosal regeneration in IBD.
AB - © 2017 The Authors 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 Iα REG Iβ REG III, HIP/PAP, and REG IV) in biopsy specimens of UC and CD by real-time RT-PCR. REG Iα REG Iβ 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 Iα REG Iβ and REG IV genes in human colon cells. The expression of REG Iα was significantly induced by IL-6 or IL-22, and REG Iβ was induced by IL-22. Deletion analyses revealed that three regions (− 220 to − 211, − 179 to − 156, and − 146 to − 130) in REG Iα and the region (− 274 to− 260) in REG Iβ 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 Iα and HLTF/FOXN2F in REG Iβ respectively. The introduction of siRNAs for MZF1, RTEF1/TEAD4, STAT3, and HLTF/FOXN2F abolished the transcription of REG Iα and REG Iβ. The gene activation mechanisms of REG Iα/REG Iβ may play a role in colon mucosal regeneration in IBD.
KW - Celiac disease
KW - Crohn's disease
KW - REG family genes
KW - Transcription
KW - Ulcerative colitis
U2 - 10.1016/j.bbrep.2017.10.003
DO - 10.1016/j.bbrep.2017.10.003
M3 - Article
SN - 2405-5808
VL - 12
SP - 198
EP - 205
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
ER -
