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The expression of proinflammatory genes in epidermal keratinocytes is regulated by hydration status.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Xu, Wei Jia, Shengxian Xie, Ping Zhong, Aimei Galiano, Robert D. Mustoe, Thomas A. Hong, Seok J.
Description	Country affiliation: United States Author Affiliation: Xu W ( Laboratory for Wound Repair and Regenerative Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Jia S ( Laboratory for Wound Repair and Regenerative Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Xie P ( Laboratory for Wound Repair and Regenerative Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Zhong A ( 1] Laboratory for Wound Repair and Regenerative Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA [2] Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.); Galiano RD ( Laboratory for Wound Repair and Regenerative Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Mustoe TA ( Laboratory for Wound Repair and Regenerative Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Hong SJ ( Laboratory for Wound Repair and Regenerative Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.)
Abstract	Mucosal wounds heal more rapidly, exhibit less inflammation, and are associated with minimal scarring when compared with equivalent cutaneous wounds. We previously demonstrated that cutaneous epithelium exhibits an exaggerated response to injury compared with mucosal epithelium. We hypothesized that treatment of injured skin with a semiocclusive dressing preserves the hydration of the skin and results in a wound healing phenotype that more closely resembles that of mucosa. Here we explored whether changes in hydration status alter epidermal gene expression patterns in rabbit partial-thickness incisional wounds. Using microarray studies on injured epidermis, we showed that global gene expression patterns in highly occluded versus non-occluded wounds are distinct. Many genes including IL-1ß, IL-8, TNF- (tumor necrosis factor- ), and COX-2 (cyclooxygenase 2) are upregulated in non-occluded wounds compared with highly occluded wounds. In addition, decreased levels of hydration resulted in an increased expression of proinflammatory genes in human ex vivo skin culture (HESC) and stratified keratinocytes. Hierarchical analysis of genes using RNA interference showed that both TNF- and IL-1ß regulate the expression of IL-8 through independent pathways in response to reduced hydration. Furthermore, both gene knockdown and pharmacological inhibition studies showed that COX-2 mediates the TNF- /IL-8 pathway by increasing the production of prostaglandin E2 (PGE2). IL-8 in turn controls the production of matrix metalloproteinase-9 in keratinocytes. Our data show that hydration status directly affects the expression of inflammatory signaling in the epidermis. The identification of genes involved in the epithelial hydration pathway provides an opportunity to develop strategies to reduce scarring and optimize wound healing.
File Format	HTM / HTML
ISSN	0022202X
e-ISSN	15231747
Journal	Journal of Investigative Dermatology
Issue Number	4
Volume Number	134
Language	English
Publisher	Elsevier
Publisher Date	2014-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Dermatology Epidermis Cytology Gene Expression Regulation Inflammation Genetics Keratinocytes Metabolism Skin Animals Cyclooxygenase 2 Dinoprostone Gene Expression Profiling Interleukin-1beta Interleukin-8 Matrix Metalloproteinase 9 Mucous Membrane Oligonucleotide Array Sequence Analysis Rna Interference Rna, Small Interfering Rabbits Signal Transduction Tumor Necrosis Factor-alpha Wound Healing Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology Dermatology

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