Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/β-catenin signaling in mice.
Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/β-catenin signaling in mice.
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巨噬细胞衍生的 EDA-A2 通过靶向小鼠中的 miR-494/EDA2R/β-连环蛋白信号抑制肠道干细胞
DOI：
10.1038/s42003-021-01730-0
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发表时间：
2021-02-16
影响因子：
5.9
通讯作者：
Zhan L
中科院分区：
文献类型：
--
作者：
Song L;Chang R;Sun X;Lu L;Gao H;Lu H;Lin R;Xu X;Liu Z;Zhan L
粘膜微环境对于炎症性肠病（IBD）中肠干细胞自我更新和上皮屏障重建至关重要，其中肠隐窝和微环境之间的串扰的潜在机制尚不清楚。在此，我们首次发现miR-494- 3 p是结肠炎的重要保护因子。miR-494- 3 p水平降低，并与人IBD样品以及结肠炎小鼠中的严重程度呈负相关。在结肠炎隐窝中，一种值得注意的丝氨酸-细胞因子受体，miR-494- 3 p靶向的EDA 2 R和配体EDA-A2，通过抑制β-连环蛋白/c-Myc抑制结肠干性和上皮修复。在分化的IEC中，miR-494- 3 p通过靶向结肠炎中的IKKβ/NF-κB抑制巨噬细胞募集、M1活化和EDA-A2分泌。miR-494- 3 p agomir系统显著改善了体内结肠炎的严重程度。总的来说，我们的研究结果揭示了miR-494- 3 p介导的串扰机制，通过该机制，巨噬细胞诱导的肠道干细胞损伤加重了肠道炎症。
The mucosa microenvironment is critical for intestinal stem cell self-renewal and reconstruction of the epithelial barrier in inflammatory bowel disease (IBD), where the mechanisms underlying cross-talk between intestinal crypts and the microenvironment remain unclear. Here, we firstly identified miR-494-3p as an important protector in colitis. miR-494-3p levels were decreased and negatively correlated with the severity in human IBD samples, as well as in colitis mice. In colitis crypts, a notable cytokine–cytokine receptor, miR-494-3p-targeted EDA2R and the ligand EDA-A2, suppressed colonic stemness and epithelial repair by inhibiting β-catenin/c-Myc. In differentiated IECs, miR-494-3p inhibits macrophage recruitment, M1 activation and EDA-A2 secretion by targeting IKKβ/NF-κB in colitis. A miR-494-3p agomir system notably ameliorated the severity of colonic colitis in vivo. Collectively, our findings uncover a miR-494-3p-mediated cross-talk mechanism by which macrophage-induced intestinal stem cell impairment aggravates intestinal inflammation.
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影响因子：
3.7
作者：
Cosín-Roger J;Ortiz-Masiá D;Calatayud S;Hernández C;Alvarez A;Hinojosa J;Esplugues JV;Barrachina MD
通讯作者：
Barrachina MD
影响因子：
64.5
作者：
Kinchen J;Chen HH;Parikh K;Antanaviciute A;Jagielowicz M;Fawkner-Corbett D;Ashley N;Cubitt L;Mellado-Gomez E;Attar M;Sharma E;Wills Q;Bowden R;Richter FC;Ahern D;Puri KD;Henault J;Gervais F;Koohy H;Simmons A
通讯作者：
Simmons A
影响因子：
4.8
作者：
Sinha, SK;Zachariah, S;Chaudhary, PM
通讯作者：
Chaudhary, PM
影响因子：
5.2
作者：
Tanikawa, Chizu;Ri, Cui;Matsuda, Koichi
通讯作者：
Matsuda, Koichi
影响因子：
24.5
作者：
Bauer, Christian;Duewell, Peter;Schnurr, Max
通讯作者：
Schnurr, Max