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Desmoglein isoform distribution affects stratum corneum structure and function.

Elias PM, Matsuyoshi N, Wu H, Lin C, Wang ZH, Brown BE, Stanley JR - J. Cell Biol. (2001)

Bottom Line: Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes.This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping.These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.

ABSTRACT
Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

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Western blot of major differentiation markers from two different involucrin-Dsg 3 mice (tg) and two control littermates (wt) show no consistent differences in expression. Filaggrin expression was variable, probably due to different amounts of retained stratum corneum or different efficiencies of extraction.
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Figure 8: Western blot of major differentiation markers from two different involucrin-Dsg 3 mice (tg) and two control littermates (wt) show no consistent differences in expression. Filaggrin expression was variable, probably due to different amounts of retained stratum corneum or different efficiencies of extraction.

Mentions: To rule out the possibility that the expression of Dsg 3 in the superficial epidermis might have major effects on multiple pathways of differentiation in the epidermis, we determined expression of loricrin, involucrin, filaggrin, and K10 in the transgenic and normal epidermis by Western blotting (Fig. 8). There were no major changes seen in the expression of these differentiation molecules. These data show that the expression of Dsg 3 in the superficial epidermis does not cause a generalized perturbation in the overall differentiation of epidermis, although we cannot rule out more subtle changes.


Desmoglein isoform distribution affects stratum corneum structure and function.

Elias PM, Matsuyoshi N, Wu H, Lin C, Wang ZH, Brown BE, Stanley JR - J. Cell Biol. (2001)

Western blot of major differentiation markers from two different involucrin-Dsg 3 mice (tg) and two control littermates (wt) show no consistent differences in expression. Filaggrin expression was variable, probably due to different amounts of retained stratum corneum or different efficiencies of extraction.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169464&req=5

Figure 8: Western blot of major differentiation markers from two different involucrin-Dsg 3 mice (tg) and two control littermates (wt) show no consistent differences in expression. Filaggrin expression was variable, probably due to different amounts of retained stratum corneum or different efficiencies of extraction.
Mentions: To rule out the possibility that the expression of Dsg 3 in the superficial epidermis might have major effects on multiple pathways of differentiation in the epidermis, we determined expression of loricrin, involucrin, filaggrin, and K10 in the transgenic and normal epidermis by Western blotting (Fig. 8). There were no major changes seen in the expression of these differentiation molecules. These data show that the expression of Dsg 3 in the superficial epidermis does not cause a generalized perturbation in the overall differentiation of epidermis, although we cannot rule out more subtle changes.

Bottom Line: Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes.This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping.These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.

ABSTRACT
Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

Show MeSH
Related in: MedlinePlus