| First Author | Kress E | Year | 2008 |
| Journal | Mol Endocrinol | Volume | 22 |
| Issue | 1 | Pages | 47-55 |
| PubMed ID | 17872380 | Mgi Jnum | J:130002 |
| Mgi Id | MGI:3770564 | Doi | 10.1210/me.2007-0278 |
| Citation | Kress E, et al. (2008) The Thyroid Hormone Receptor-{alpha} (TR{alpha}) Gene Encoding TR{alpha}1 Controls Deoxyribonucleic Acid Damage-Induced Tissue Repair. Mol Endocrinol 22(1):47-55 |
| abstractText | The thyroid hormone (TH) controls, via its nuclear receptor, TH receptor-alpha1 (TRalpha1), intestinal crypt cell proliferation in the mouse. In order to understand whether this receptor also plays a role in intestinal regeneration after DNA damage, we applied a protocol of gamma-ray irradiation and monitored cell proliferation and apoptosis at several time points. In wild-type mice, the dose of 8 Gy induced cell cycle arrest and apoptosis in intestinal crypts a few hours after irradiation. This phenomenon reverted 48 h after irradiation. TRalpha(0/0) mutant mice displayed a constant low level of proliferating cells and a high apoptosis rate during the period of study. At the molecular level, in TRalpha(0/0) animals we observed a delay in the p53 phosphorylation induced by DNA damage. In our search for the expression of the protein kinases responsible for p53 phosphorylation upon irradiation, we have focused on DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The number of cells expressing DNA-PKcs in crypts remained high 48 h after irradiation, specifically in TRalpha mutants. Altogether, in TRalpha(0/0) animals the rate of apoptosis in crypt cells remained high, apparently due to an elevated number of cells still presenting DNA damage. In conclusion, the TRalpha gene plays a role in crypt cell homeostasis by regulating the rate of cell renewal and apoptosis induced by DNA damage. |
