| Literature DB >> 33490652 |
Reiko Kuno1, Go Ito2, Ami Kawamoto1, Yui Hiraguri1, Hady Yuki Sugihara1, Sayaka Takeoka1, Sayaka Nagata1, Junichi Takahashi1, Mao Tsuchiya1, Sho Anzai1, Tomohiro Mizutani1, Hiromichi Shimizu3, Shiro Yui3, Shigeru Oshima1, Kiichiro Tsuchiya1, Mamoru Watanabe2, Ryuichi Okamoto1,3.
Abstract
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. We confirmed that TNF-α and Notch synergistically upregulate the mRNA expression of OLFM4. Luciferase reporter assay showed that OLFM4 transcription is regulated by the synergy of TNF-α and Notch. At the protein level, synergy between TNF-α and Notch promoted cytoplasmic accumulation of OLFM4, which has potential anti-apoptotic properties in human IECs. Analysis of patient-derived tissues and organoids consistently showed cytoplasmic accumulation of OLFM4 in response to NF-κB and Notch activation. Cytoplasmic accumulation of OLFM4 in human IECs is tightly regulated by Notch and TNF-α in synergy. Such cytoplasmic accumulation of OLFM4 may have a cell-protective role in the inflamed mucosa of patients with IBD.Entities:
Keywords: CD, Crohn's disease; ChIP, chromatin immunoprecipitation; DBZ, intestinal epithelial cells; Dox, doxycycline; IBD, inflammatory bowel disease; IEC, dibenzazepine; NICD, Notch intracellular domain; Notch pathway; OLFM4; TNF-α, tumour necrosis factor α; Tumour necrosis factor-α (TNF-α); UC, ulcerative colitis; qRT-PCR, quantitative reverse transcription-polymerase chain reaction analysis
Year: 2021 PMID： 33490652 PMCID： PMC7808948 DOI： 10.1016/j.bbrep.2020.100906
Source DB: PubMed Journal: Biochem Biophys Rep ISSN： 2405-5808