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Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/?-catenin signaling in mice.

ABSTRACT: 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 ?-catenin/c-Myc. In differentiated IECs, miR-494-3p inhibits macrophage recruitment, M1 activation and EDA-A2 secretion by targeting IKK?/NF-?B 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.

SUBMITTER: Song L

PROVIDER: S-EPMC7887198 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/β-catenin signaling in mice.

Song Lele L Chang Renxu R Sun Xia X Lu Liying L Gao Han H Lu Huiying H Lin Ritian R Xu Xiaorong X Liu Zhanju Z Zhan Lixing L

Communications biology 20210216 1

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 notab ...[more]

PMID: 33594251

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Dataset Information

Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/?-catenin signaling in mice.

Publications

Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/β-catenin signaling in mice.

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