| RXRα ablation in epidermal keratinocytes enhances UVR-induced DNA damage, apoptosis, and proliferation of keratinocytes and melanocytes. | |
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MedLine Citation:
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PMID: 20944655 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We show here that keratinocytic nuclear receptor retinoid X receptor-α (RXRα) regulates mouse keratinocyte and melanocyte homeostasis following acute UVR. Keratinocytic RXRα has a protective role in UVR-induced keratinocyte and melanocyte proliferation/differentiation, oxidative stress-mediated DNA damage, and cellular apoptosis. We discovered that keratinocytic RXRα, in a cell-autonomous manner, regulates mitogenic growth responses in skin epidermis through secretion of heparin-binding EGF-like growth factor, GM-CSF, IL-1α, 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, α-melanocyte stimulating hormone, stem cell factor, and fibroblast growth factor-2 in skin of mice lacking RXRα in epidermal keratinocytes (RXRα(ep-/-) mice), which in a non-cell-autonomous manner modulated melanocyte proliferation and activation after UVR. RXRα(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. |
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Authors:
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Zhixing Wang; Daniel J Coleman; Gaurav Bajaj; Xiaobo Liang; Gitali Ganguli-Indra; Arup K Indra |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-14 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: 131 ISSN: 1523-1747 ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-15 Completed Date: 2011-01-24 Revised Date: 2012-01-04 |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 177-87 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology, radiation effects Autocrine Communication / physiology, radiation effects Cell Communication / physiology, radiation effects Cell Differentiation / physiology, radiation effects Cell Division / physiology, radiation effects Cells, Cultured Culture Media, Conditioned / pharmacology DNA Adducts / radiation effects DNA Damage / physiology* Epidermis / cytology, physiology, radiation effects Homeostasis / physiology, radiation effects Keratinocytes* / cytology, physiology, radiation effects Melanocytes* / cytology, physiology, radiation effects Mice Mice, Inbred C57BL Mice, Transgenic Retinoid X Receptor alpha / genetics*, metabolism Ultraviolet Rays / adverse effects* |
| Grant Support | |
ID/Acronym/Agency:
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ES00210/ES/NIEHS NIH HHS; ES016629-01A1/ES/NIEHS NIH HHS; R01 ES016629-02/ES/NIEHS NIH HHS; R01 ES016629-03/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Culture Media, Conditioned; 0/DNA Adducts; 0/Retinoid X Receptor alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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