Notch and TNF-α signaling promote cytoplasmic accumulation of OLFM4 in intestinal epithelium cells and exhibit a cell protective role in the inflamed mucosa of IBD patients.

Notch signaling is activated in the intestinal epithelial cells (IECs) of patients with inflammatory bowel disease (IBD), and contributes to mucosal regeneration. Our previous study indicated that TNF-α and Notch signaling may synergistically promote the expression of the intestinal stem cell (ISC) marker OLFM4 in human IECs. In the present study, we investigated the gene regulation and function of OLFM4 in human IEC lines.

Functional analysis of isoflavones using patient-derived human colonic organoids.

Inflammatory bowel disease (IBD) comprises two major subtypes, ulcerative colitis (UC) and Crohn's disease, which are multifactorial diseases that may develop due to genetic susceptibility, dysbiosis, or environmental factors. Environmental triggers of IBD include food-borne factors, and a previous nationwide survey in Japan identified pre-illness consumption of isoflavones as a risk factor for UC. However, the precise mechanisms involved in the detrimental effects of isoflavones on the intestinal mucosa remain unclear.

TGF-β promotes fetal gene expression and cell migration velocity in a wound repair model of untransformed intestinal epithelial cells.

The early-phase wound repair response of the intestinal epithelium is characterized by rapid and organized cell migration. This response is regulated by several humoral factors, including TGF-β. However, due to a lack of appropriate models, the precise response of untransformed intestinal epithelial cells (IECs) to those factors is unclear.

Ubiquitin D is Upregulated by Synergy of Notch Signalling and TNF-α in the Inflamed Intestinal Epithelia of IBD Patients.

Background And Aims: The intestinal epithelium of inflammatory bowel disease [IBD] patients is exposed to various pro-inflammatory cytokines, most notably tumour necrosis factor alpha [TNF-α]. We have previously shown that the Notch signalling pathway is also upregulated in such an epithelium, contributing to intestinal epithelial cell [IEC] proliferation and regeneration. We aimed to reproduce such environment in vitro and explore the gene regulation involved.

Single cell analysis of Crohn's disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties.

Background: Intestinal stem cells (ISCs) play indispensable roles in the maintenance of homeostasis, and also in the regeneration of the damaged intestinal epithelia. However, whether the inflammatory environment of Crohn's disease (CD) affects properties of resident small intestinal stem cells remain uncertain.

Methods: CD patient-derived small intestinal organoids were established from enteroscopic biopsy specimens taken from active lesions (aCD-SIO), or from mucosa under remission (rCD-SIO).

Contribution of ATOH1 Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium.

ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, the comprehensive contribution of ATOH1 secretory lineage IECs to the homeostasis, repair, and tumorigenesis of the intestinal epithelium remains uncertain. Through our ATOH1 cell-lineage tracing, we show here that a definite number of ATOH1 IECs retain stem cell properties and can form ATOH1IEC-derived clonal ribbons (ATOH1ICRs) under completely homeostatic conditions.

Data showing proliferation and differentiation of intestinal epithelial cells under targeted depletion of Notch ligands in mouse intestine.

The data on the immunohistochemical analysis of conditional Notch ligand knockout mice is presented. Targeted deletion of or plus in Lgr5 cells was induced by a Cre-mediated gene recombination, and differentiation or proliferation of the intestinal epithelial cells was examined by immunohistochemistry. These data are the extension of the data presented and discussed in the paper entitled "Indispensable role of non-canonical Notch signaling in the proliferation of Apc-deficient intestinal tumors" (Nakata et al.

Indispensable role of Notch ligand-dependent signaling in the proliferation and stem cell niche maintenance of APC-deficient intestinal tumors.

Ligand-dependent activation of Notch signaling is required to maintain the stem-cell niche of normal intestinal epithelium. However, the precise role of Notch signaling in the maintenance of the intestinal tumor stem cell niche and the importance of the RBPJ-independent non-canonical pathway in intestinal tumors remains unknown. Here we show that Notch signaling was activated in LGR5 cells of APC-deficient mice intestinal tumors.

Efficacy of short period, low dose oral prednisolone for the prevention of stricture after circumferential endoscopic submucosal dissection (ESD) for esophageal cancer.

Background And Aims: Endoscopic submucosal dissection (ESD) was developed in Japan and has been performed on many patients with early stage esophageal cancer; however quality of life in patients with postoperative stricture is drastically decreased and repeat, periodic endoscopic balloon dilatation (EBD) is usually required over long periods. In this study, we evaluate the efficacy of short period, low dose oral prednisolone in controlling post-procedural esophageal stricture.

Patients And Methods: In total, 33 patients who underwent semicircular or complete circular ESD for esophageal superficial squamous cell carcinoma were included in this study.