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Superficial dsg2 expression limits epidermal blister formation mediated by pemphigus foliaceus antibodies and exfoliative toxins.

Brennan D, Hu Y, Medhat W, Dowling A, Mahoney MG - Dermatol Res Pract (2010)

Bottom Line: Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins.We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig.Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.

ABSTRACT
Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig. In response to PF Ig, we observed either a dramatic loss or a reorganization of Dsg1-alpha, Dsg1-beta, and, to a lesser extent, Dsg1-gamma, in WT mice. The Inv-Dsg2 Tg mice showed enhanced retention of Dsg1 at the cell-cell border. Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.

No MeSH data available.


Related in: MedlinePlus

Suprabasal expression of Dsg2-Flag in newborn Inv-Dsg2 transgenic mice. (a) Histology showing slight epidermal hyperplasia in a newborn Inv-Dsg2 Tg overexpressing Dsg2 in the superficial epidermis under the involucrin promoter, but not in WT mice. (b) Immunostaining of newborn Tg skin with Flag (green) and Dsg2-specific MP6 (red) antibodies showing expression of Dsg2-Flag in the differentiated cell layers of the transgenic epidermis. (c) Immunoblot of WT and Tg skin with MP6 and Flag antibodies, showing Dsg2-Flag in the Tg but not WT skin. Actin was used for equal loading.
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fig1: Suprabasal expression of Dsg2-Flag in newborn Inv-Dsg2 transgenic mice. (a) Histology showing slight epidermal hyperplasia in a newborn Inv-Dsg2 Tg overexpressing Dsg2 in the superficial epidermis under the involucrin promoter, but not in WT mice. (b) Immunostaining of newborn Tg skin with Flag (green) and Dsg2-specific MP6 (red) antibodies showing expression of Dsg2-Flag in the differentiated cell layers of the transgenic epidermis. (c) Immunoblot of WT and Tg skin with MP6 and Flag antibodies, showing Dsg2-Flag in the Tg but not WT skin. Actin was used for equal loading.

Mentions: As previously described in detail, we generated Tg mice expressing Dsg2 in the superficial epidermis, under the control of the involucrin promoter [14]. Newborn Tg mice appeared normal, with no gross abnormalities of the skin or hair. Examination of the skin by histology revealed minor epidermal hyperplasia in newborn Tg mice compared to WT littermates (Figure 1(a)). We assessed the expression of the Dsg2-Flag transgene in skin from newborn Tg mice by immunostaining; antibodies against Flag and Dsg2 (MP6) (Figure 1(b)) showed expression of Dsg2-Flag in the superficial cell layers. In keeping with the literature, we observed some negligible expression of endogenous Dsg2 in the basal cell layer.


Superficial dsg2 expression limits epidermal blister formation mediated by pemphigus foliaceus antibodies and exfoliative toxins.

Brennan D, Hu Y, Medhat W, Dowling A, Mahoney MG - Dermatol Res Pract (2010)

Suprabasal expression of Dsg2-Flag in newborn Inv-Dsg2 transgenic mice. (a) Histology showing slight epidermal hyperplasia in a newborn Inv-Dsg2 Tg overexpressing Dsg2 in the superficial epidermis under the involucrin promoter, but not in WT mice. (b) Immunostaining of newborn Tg skin with Flag (green) and Dsg2-specific MP6 (red) antibodies showing expression of Dsg2-Flag in the differentiated cell layers of the transgenic epidermis. (c) Immunoblot of WT and Tg skin with MP6 and Flag antibodies, showing Dsg2-Flag in the Tg but not WT skin. Actin was used for equal loading.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902105&req=5

fig1: Suprabasal expression of Dsg2-Flag in newborn Inv-Dsg2 transgenic mice. (a) Histology showing slight epidermal hyperplasia in a newborn Inv-Dsg2 Tg overexpressing Dsg2 in the superficial epidermis under the involucrin promoter, but not in WT mice. (b) Immunostaining of newborn Tg skin with Flag (green) and Dsg2-specific MP6 (red) antibodies showing expression of Dsg2-Flag in the differentiated cell layers of the transgenic epidermis. (c) Immunoblot of WT and Tg skin with MP6 and Flag antibodies, showing Dsg2-Flag in the Tg but not WT skin. Actin was used for equal loading.
Mentions: As previously described in detail, we generated Tg mice expressing Dsg2 in the superficial epidermis, under the control of the involucrin promoter [14]. Newborn Tg mice appeared normal, with no gross abnormalities of the skin or hair. Examination of the skin by histology revealed minor epidermal hyperplasia in newborn Tg mice compared to WT littermates (Figure 1(a)). We assessed the expression of the Dsg2-Flag transgene in skin from newborn Tg mice by immunostaining; antibodies against Flag and Dsg2 (MP6) (Figure 1(b)) showed expression of Dsg2-Flag in the superficial cell layers. In keeping with the literature, we observed some negligible expression of endogenous Dsg2 in the basal cell layer.

Bottom Line: Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins.We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig.Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.

ABSTRACT
Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig. In response to PF Ig, we observed either a dramatic loss or a reorganization of Dsg1-alpha, Dsg1-beta, and, to a lesser extent, Dsg1-gamma, in WT mice. The Inv-Dsg2 Tg mice showed enhanced retention of Dsg1 at the cell-cell border. Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.

No MeSH data available.


Related in: MedlinePlus