| First Author | Contreras-Jurado C | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 27 | Pages | 24079-88 |
| PubMed ID | 21566120 | Mgi Jnum | J:175277 |
| Mgi Id | MGI:5285057 | Doi | 10.1074/jbc.M111.218487 |
| Citation | Contreras-Jurado C, et al. (2011) The thyroid hormone receptors as modulators of skin proliferation and inflammation. J Biol Chem 286(27):24079-88 |
| abstractText | We have analyzed the role of the thyroid hormone receptors (TRs) in epidermal homeostasis. Reduced keratinocyte proliferation is found in interfollicular epidermis of mice lacking the thyroid hormone binding isoforms TRalpha1 and TRbeta (KO mice). Similar results were obtained in hypothyroid animals, showing the important role of the liganded TRs in epidermal proliferation. In addition, KO and hypothyroid animals display decreased hyperplasia in response to 12-O-tetradecanolyphorbol-13-acetate. Both receptor isoforms play overlapping functional roles in the skin because mice lacking individually TRalpha1 or TRbeta also present a proliferative defect but not as marked as that found in double KO mice. Defective proliferation in KO mice is associated with reduction of cyclin D1 expression and up-regulation of the cyclin-dependent kinase inhibitors p19 and p27. Paradoxically, ERK and AKT activity and expression of downstream targets, such as AP-1 components, are increased in KO mice. Increased p65/NF-kappaB and STAT3 phosphorylation and, as a consequence, augmented expression of chemokines and proinflammatory cytokines is also found in these animals. These results show that thyroid hormones and their receptors are important mediators of skin proliferation and demonstrate that TRs act as endogenous inhibitors of skin inflammation, most likely due to interference with AP-1, NF-kappaB, and STAT3 activation. |
