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 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.
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Notch和TNF-α信号促进OLFM 4在肠上皮细胞中的细胞质积累，并在IBD患者的炎症粘膜中表现出细胞保护作用。
DOI：
10.1016/j.bbrep.2020.100906
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发表时间：
2021-03
影响因子：
2.7
通讯作者：
Okamoto R
中科院分区：
文献类型：
--
作者：
Kuno R;Ito G;Kawamoto A;Hiraguri Y;Sugihara HY;Takeoka S;Nagata S;Takahashi J;Tsuchiya M;Anzai S;Mizutani T;Shimizu H;Yui S;Oshima S;Tsuchiya K;Watanabe M;Okamoto R
Notch信号在患有炎症性肠病（IBD）的患者的肠上皮细胞（IEC）中被激活，并且有助于粘膜再生。我们的前期研究表明TNF-α和Notch信号可能协同促进肠干细胞（ISC）标志物OLFM 4在人IEC中的表达。在本研究中，我们研究了OLFM 4在人类IEC系中的基因调控和功能。我们证实TNF-α和Notch协同上调OLFM 4的mRNA表达。荧光素酶报告基因分析表明，OLFM 4的转录受TNF-α和Notch的协同调控。在蛋白质水平，TNF-α和Notch之间的协同作用促进了OLFM 4的细胞质积累，OLFM 4在人IEC中具有潜在的抗凋亡特性。患者来源的组织和类器官的分析一致地显示响应于NF-κB和Notch活化的OLFM 4的细胞质积累。人IEC中OLFM 4的胞质积累受Notch和TNF-α协同作用的严格调节。OLFM 4的这种细胞质积累可能在IBD患者的发炎粘膜中具有细胞保护作用。Notch和TNF-α信号在IBD患者的IEC中是重要的。Notch和TNF-α信号传导促进OLFM 4的细胞质积累。OLFM 4积累可能具有抗凋亡特性。OLFM 4对IBD的黏膜炎症有保护作用。
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. Notch and TNF-α signaling is important in IECs of patients with IBD. Notch and TNF-α signaling promotes the cytoplasmic accumulation of OLFM4. OLFM4 accumulation may have anti-apoptotic properties. OLFM4 could protect against mucosal inflammation in IBD.
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影响因子：
24.5
作者：
Reynolds A;Wharton N;Parris A;Mitchell E;Sobolewski A;Kam C;Bigwood L;El Hadi A;Münsterberg A;Lewis M;Speakman C;Stebbings W;Wharton R;Sargen K;Tighe R;Jamieson C;Hernon J;Kapur S;Oue N;Yasui W;Williams MR
通讯作者：
Williams MR
影响因子：
4.6
作者：
VanDussen, Kelli L.;Carulli, Alexis J.;Samuelson, Linda C.
通讯作者：
Samuelson, Linda C.
影响因子：
5.9
作者：
Schuijers, Jurian;van der Flier, Laurens G.;van Es, Johan;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
64.8
作者：
Khor, Bernard;Gardet, Agnes;Xavier, Ramnik J.
通讯作者：
Xavier, Ramnik J.
影响因子：
7
作者：
Besson, Damien;Pavageau, Aude-Helene;Guette, Catherine
通讯作者：
Guette, Catherine