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首页> 外文期刊>International Journal of Molecular Sciences >NOD2 Supports Crypt Survival and Epithelial Regeneration after Radiation-Induced Injury
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NOD2 Supports Crypt Survival and Epithelial Regeneration after Radiation-Induced Injury

机译:NOD2支持辐射致伤害后的隐窝生存和上皮再生。

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Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) affords stem cell protection and links microbes to intestinal epithelial regeneration. We investigated whether NOD2 status is associated with crypt survival and intestinal epithelial regeneration independent of microbiota-derived molecules. To assess crypt survival, a clonogenic microcolony assay was performed with 15 Gy of X-ray irradiation. The fractional crypt survival rate (46.0 ± 15.5% vs. 24.7 ± 9.2%, p 0.01) and fractional EdU-positive crypt survival rate (29.8 ± 14.5% vs. 9.79 ± 4.37%, p = 0.015) were significantly decreased in the NOD2 ?/? mice compared with the wild-type (WT) mice at 3.5 days after irradiation. To evaluate intestinal epithelial regeneration capability, organoid reconstitution assays were performed. Small bowel crypts of the WT and NOD2 ?/? mice were isolated and seeded into Matrigel for 3D culture. In the organoid reconstitution assays, the number of organoids formed did not differ between the NOD2 ?/? and WT mice. Organoid formation ability was also assessed after exposure to 5 Gy irradiation. Organoid formation ability was significantly decreased in the NOD2 ?/? mice compared with the WT ones after exposure to 5 Gy irradiation (33.2 ± 5.9 vs. 19.7 ± 8.8/well, p 0.01). NOD2 supports crypt survival after potentially lethal irradiation damage and is associated with intestinal epithelial regeneration.
机译:含有核苷酸结合的寡聚域的蛋白质2(NOD2)提供干细胞保护并将微生物与肠道上皮再生联系起来。我们调查了NOD2状态是否与隐窝生存和独立于微生物群的分子的肠上皮再生相关。为了评估隐窝的存活,用15 Gy的X射线进行了克隆形成的微菌落测定。隐窝存活率(46.0±15.5%vs. 24.7±9.2%,p <0.01)和EdU阳性隐窝存活率(29.8±14.5%vs 9.79±4.37%,p = 0.015)显着降低。 NOD2?/?照射后3.5天,将小鼠与野生型(WT)小鼠进行比较。为了评估肠上皮再生能力,进行了类器官重建试验。 WT和NOD2?/?的小肠隐窝。分离小鼠并将其接种到Matrigel中进行3D培养。在类器官重建试验中,形成的类器官数目在NOD2α/β之间没有差异。和野生型小鼠。暴露于5 Gy辐射后,还评估了类器官形成能力。 NOD2α/β中类器官形成能力显着降低。暴露于5 Gy辐射下的小鼠与野生型小鼠相比(33.2±5.9对19.7±8.8 /孔,p <0.01)。 NOD2支持潜在致死性辐射损伤后的隐窝存活,并与肠道上皮再生有关。

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