| First Author | Wang Z | Year | 2011 |
| Journal | J Invest Dermatol | Volume | 131 |
| Issue | 1 | Pages | 177-87 |
| PubMed ID | 20944655 | Mgi Jnum | J:180849 |
| Mgi Id | MGI:5307974 | Doi | 10.1038/jid.2010.290 |
| Citation | Wang Z, et al. (2011) RXRalpha ablation in epidermal keratinocytes enhances UVR-induced DNA damage, apoptosis, and proliferation of keratinocytes and melanocytes. J Invest Dermatol 131(1):177-87 |
| abstractText | We show here that keratinocytic nuclear receptor retinoid X receptor-alpha (RXRalpha) regulates mouse keratinocyte and melanocyte homeostasis following acute UVR. Keratinocytic RXRalpha has a protective role in UVR-induced keratinocyte and melanocyte proliferation/differentiation, oxidative stress-mediated DNA damage, and cellular apoptosis. We discovered that keratinocytic RXRalpha, in a cell-autonomous manner, regulates mitogenic growth responses in skin epidermis through secretion of heparin-binding EGF-like growth factor, GM-CSF, IL-1alpha, and cyclooxygenase-2 and activation of mitogen-activated protein kinase pathways. We identified altered expression of several keratinocyte-derived mitogenic paracrine growth factors such as endothelin 1, hepatocyte growth factor, alpha-melanocyte stimulating hormone, stem cell factor, and fibroblast growth factor-2 in skin of mice lacking RXRalpha in epidermal keratinocytes (RXRalpha(ep-/-) mice), which in a non-cell-autonomous manner modulated melanocyte proliferation and activation after UVR. RXRalpha(ep-/-) mice represent a unique animal model in which UVR induces melanocyte proliferation/activation in both epidermis and dermis. Considered together, the results of our study suggest that RXR antagonists, together with inhibitors of cell proliferation, can be effective in preventing solar UVR-induced photocarcinogenesis. |
