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

ABSTRACT: 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 I?, REG I?, REG III, HIP/PAP, and REG IV) in biopsy specimens of UC and CD by real-time RT-PCR. REG I?, REG I?, 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 I?, REG I?, and REG IV genes in human colon cells. The expression of REG I? was significantly induced by IL-6 or IL-22, and REG I? was induced by IL-22. Deletion analyses revealed that three regions (- 220 to - 211, - 179 to - 156, and - 146 to - 130) in REG I? and the region (- 274 to- 260) in REG I? 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 I?, and HLTF/FOXN2F in REG I?, respectively. The introduction of siRNAs for MZF1, RTEF1/TEAD4, STAT3, and HLTF/FOXN2F abolished the transcription of REG I? and REG I?. The gene activation mechanisms of REG I?/REG I? may play a role in colon mucosal regeneration in IBD.

SUBMITTER: Tsuchida C

PROVIDER: S-EPMC5655384 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Tsuchida Chikatsugu C Sakuramoto-Tsuchida Sumiyo S Taked Maiko M Itaya-Hironaka Asako A Yamauchi Akiyo A Misu Masayasu M Shobatake Ryogo R Uchiyama Tomoko T Makino Mai M Pujol-Autonell Irma I Vives-Pi Marta M Ohbayashi Chiho C Takasawa Shin S

Biochemistry and biophysics reports 20171023

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 ...[more]

PMID: 29090282

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Project description:In this review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and noncoding genetic variation. In the small minority of loci where major association signals correspond to nonsynonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve noncoding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that the expression of most human genes is regulated by noncoding genetic variations. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (ie, odds ratios markedly deviating from 1) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in more severe very early onset cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility through emerging precision medical initiatives. In this article, we discuss the rapidly evolving area of direct-to-consumer genetic testing and the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect to partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD.

Dataset Information

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

Publications

Expression of <i>REG</i> family genes in human inflammatory bowel diseases and its regulation.

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