Epidermal aquaporin-3 is increased in the cutaneous burn wound
Introduction
Aquaporins (AQP) are a family of transmembrane proteins that transport water and small solutes such as glycerol across cell membranes [1]. It is a mediator of transcellular water flow and plays an important role in maintaining intra/extracellular fluid homeostasis by facilitating water transport in response to changing osmotic gradients [2]. AQPs are found in the major systems of the human body such as the nervous, renal, cardiovascular, respiratory, reproductive, digestive, musculoskeletal, and integumentary systems [2].
In the skin, AQPs permit rapid, regulated, and selective water permeability and have been demonstrated to play a role in skin hydration, cell proliferation, migration, immunity, and wound healing [3], [4], [5]. Overall, 6 skin AQPs have been identified. At the epidermal level, the most important and abundant of these proteins is AQP-3. It is a member of the aquaglyceroporin subfamily and is found primarily in the plasma membrane of keratinocytes and dermal fibroblasts [6], [7]. AQP-3 has function in the transportation of water and glycerol, a natural moisturizing factor that keeps the skin hydrated, in the interstitial space and intracellularly [8].
In the epidermis, AQP3 is organized to create a highly selective permeability gradient (Fig. 1). For example, epidermal permeability progressively increases from the stratum corneum to the stratum basale. Not coincidentally, this difference in cell permeability is proportional to the concentration of AQP3 within each epidermal layer, with high concentrations being found in the stratum basale and absent in the stratum corneum and granulosum. In fact, it is this proportionate increase in membrane permeability to AQP3 expression that forms the biologic rationale for an AQP3 mediated water clamp or gate phenomenon, a regulatory mechanism by which water moves across cellular membranes dependent on the conformation of the protein channel in the open or closed position [9].
Wound healing in the skin is a multi-step process that involves several cell types, including epidermal keratinocytes, fibroblasts, endothelial cells, and peripheral nerve cells [10]. In addition to cellular involvement, a number of cell signaling molecules and proteins are involved in this process as well. AQP-3 is integral to wound healing by facilitating water and glycerol transport and therefore keratinocyte migration and proliferation respectively [3]. In fact, the absence of AQP3 regulated transport of water and glycerol has been shown to impair wound healing in animal models [11].
While the role of role of AQP-3 in cutaneous wound healing has been defined, its activity in the burn wound has not previously been determined. The aim of our study was to determine the effect of a cutaneous burn on AQP-3 expression within the wound.
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Materials and methods
Following institutional review board approval (IRB), a total of 7 patients were selected for our study. Full thickness biopsy samples were taken from 3 locations on each patient; the burn wound center, edge, and graft donor sites for a total of 21 specimens (3 per patient) approximately 3–7 days post injury. The areas of burn to be biopsied were determined from physical examination by an experienced burn surgeon. The samples were immediately processed and stored in alloprotect reagent (Qiagen).
Results
A total of 20 patients were enrolled into our study (N = 7) over a 5-month period. The mean age of the patients selected was 51 years (22–82 years) with 43% male and 57% female. African-Americans accounted for 29% (N = 2) of the patient population, Caucasian 57% (N = 4), Asian 14% (N = 1). The average total body surface area (TBSA) that was burned on these patients was 11.6%. The mechanism of each burn was 57% flame (N = 4), 29% scald (N = 2), and 14% grease (N = 1) (Table 1). Light microscopy of biopsied
Discussion
We sought to determine the effect of a cutaneous burn on AQP-3 expression in humans using tissue samples from patients admitted to our unit with deep burns to skin. Full thickness biopsy samples were taken from the wound edge (defined clinically as a partial thickness burn), the donor site (normal skin), and wound center (full thickness burn). We evaluated the location and the degree of AQP-3 expression in the skin using immunofluorescence and western blot analysis respectively.
In the center of
Disclosures
The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.
Author contributions
R. Sebastian, E. Chau, P. Fillmore participated in the development of the study, conducted the experiments, assisted in interpreting the data and writing the manuscript. J. Matthews served in interpreting the data, determining its clinical significance and writing the manuscript. L.A. Price and V. Sidhaye assisted in the design of the experiments and determining its clinical significance. S. Milner oversaw all aspects of the study and obtained the grant that provided funding for the study.
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