First Author | Lee C | Year | 2019 |
Journal | Int J Mol Sci | Volume | 20 |
Issue | 17 | PubMed ID | 31480799 |
Mgi Jnum | J:293526 | Mgi Id | MGI:6452890 |
Doi | 10.3390/ijms20174297 | Citation | Lee C, et al. (2019) NOD2 Supports Crypt Survival and Epithelial Regeneration after Radiation-Induced Injury. Int J Mol Sci 20(17):4297 |
abstractText | 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. |