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)...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-03-01
|
| Series: | Biochemistry and Biophysics Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580820302168 |
| _version_ | 1818870517611888640 |
|---|---|
| author | Reiko Kuno Go Ito Ami Kawamoto Yui Hiraguri Hady Yuki Sugihara Sayaka Takeoka Sayaka Nagata Junichi Takahashi Mao Tsuchiya Sho Anzai Tomohiro Mizutani Hiromichi Shimizu Shiro Yui Shigeru Oshima Kiichiro Tsuchiya Mamoru Watanabe Ryuichi Okamoto |
| author_facet | Reiko Kuno Go Ito Ami Kawamoto Yui Hiraguri Hady Yuki Sugihara Sayaka Takeoka Sayaka Nagata Junichi Takahashi Mao Tsuchiya Sho Anzai Tomohiro Mizutani Hiromichi Shimizu Shiro Yui Shigeru Oshima Kiichiro Tsuchiya Mamoru Watanabe Ryuichi Okamoto |
| author_sort | Reiko Kuno |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T12:08:17Z |
| format | Article |
| id | doaj.art-0a375b89ba1e4c71a4f4c238859107d9 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-19T12:08:17Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-0a375b89ba1e4c71a4f4c238859107d92022-12-21T20:22:17ZengElsevierBiochemistry and Biophysics Reports2405-58082021-03-0125100906Notch 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 patientsReiko Kuno0Go Ito1Ami Kawamoto2Yui Hiraguri3Hady Yuki Sugihara4Sayaka Takeoka5Sayaka Nagata6Junichi Takahashi7Mao Tsuchiya8Sho Anzai9Tomohiro Mizutani10Hiromichi Shimizu11Shiro Yui12Shigeru Oshima13Kiichiro Tsuchiya14Mamoru Watanabe15Ryuichi Okamoto16Department of Gastroenterology and Hepatology, JapanAdvanced Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanCenter for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), Tokyo, JapanCenter for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Gastroenterology and Hepatology, JapanDepartment of Gastroenterology and Hepatology, JapanAdvanced Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Gastroenterology and Hepatology, Japan; Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), Tokyo, Japan; Corresponding author. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.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.http://www.sciencedirect.com/science/article/pii/S2405580820302168Tumour necrosis factor-α (TNF-α)Notch pathwayOLFM4 |
| spellingShingle | Reiko Kuno Go Ito Ami Kawamoto Yui Hiraguri Hady Yuki Sugihara Sayaka Takeoka Sayaka Nagata Junichi Takahashi Mao Tsuchiya Sho Anzai Tomohiro Mizutani Hiromichi Shimizu Shiro Yui Shigeru Oshima Kiichiro Tsuchiya Mamoru Watanabe Ryuichi Okamoto 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 Biochemistry and Biophysics Reports Tumour necrosis factor-α (TNF-α) Notch pathway OLFM4 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Tumour necrosis factor-α (TNF-α) Notch pathway OLFM4 |
| url | http://www.sciencedirect.com/science/article/pii/S2405580820302168 |
| work_keys_str_mv | AT reikokuno notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT goito notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT amikawamoto notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT yuihiraguri notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT hadyyukisugihara notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT sayakatakeoka notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT sayakanagata notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT junichitakahashi notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT maotsuchiya notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT shoanzai notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT tomohiromizutani notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT hiromichishimizu notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT shiroyui notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT shigeruoshima notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT kiichirotsuchiya notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT mamoruwatanabe notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients AT ryuichiokamoto notchandtnfasignalingpromotecytoplasmicaccumulationofolfm4inintestinalepitheliumcellsandexhibitacellprotectiveroleintheinflamedmucosaofibdpatients |