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Cellular responses to disruption of the permeability barrier in a three-dimensional organotypic epidermal model
被引:29
作者:
Ajani, Gati
Sato, Nobuyuki
Mack, Judith A.
Maytin, Edward V.
机构:
[1] Cleveland Clin Fdn, Dept Dermatol, Cleveland, OH 44195 USA
[2] Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA
[3] Niigata Univ, Sch Med, Dept Dermatol, Niigata 9518510, Japan
关键词:
organotypic model;
barrier injury;
epidermis;
skin;
proliferation;
differentiation;
TISSUE ENGINEERED SKIN;
GENE-EXPRESSION;
DIFFERENTIATION;
HYALURONAN;
CULTURES;
KERATINOCYTES;
COLLAGEN;
LIPIDS;
ACID;
D O I:
10.1016/j.yexcr.2007.04.021
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Repeated injury to the stratum corneum of mammalian skin (caused by friction, soaps, or organic solvents) elicits hyperkeratosis and epidermal thickening. Functionally, these changes serve to restore the cutaneous barrier and protect the organism. To better understand the molecular and cellular basis of this response, we have engineered an in vitro model of acetone-induced injury using organotypic epidermal cultures. Rat epidermal keratinocytes (REKs), grown on a collagen raft in the absence of any feeder fibroblasts, developed all the hallmarks of a true epidermis including a well-formed cornified layer. To induce barrier injury, REK cultures were treated with intermittent 30-s exposures to acetone then were fixed and paraffin- sectioned. After two exposures, increased proliferation (Ki67 and BrdU staining) was observed in basal and suprabasal layers. After three exposures, proliferation became confined to localized buds in the basal layer and increased terminal differentiation was observed (compact hyperkeratosis of the stratum corneum, elevated levels of K10 and filaggrin, and heightened trans glutaminase activity). Thus, barrier disruption causes epidermal hyperplasia and/or enhances differentiation, depending upon the extent and duration of injury. Given that no fibroblasts are present in the model, the ability to mount a hyperplastic response to barrier injury is an inherent property of keratinocytes. (c) 2007 Elsevier Inc. All rights reserved.
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页码:3005 / 3015
页数:11
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