Document Detail


RXRα ablation in epidermal keratinocytes enhances UVR-induced DNA damage, apoptosis, and proliferation of keratinocytes and melanocytes.
MedLine Citation:
PMID:  20944655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Zhixing Wang; Daniel J Coleman; Gaurav Bajaj; Xiaobo Liang; Gitali Ganguli-Indra; Arup K Indra
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-14
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  131     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-15     Completed Date:  2011-01-24     Revised Date:  2012-01-04    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  177-87     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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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