Epidermal desquamation

Milstone, Leonard M.

doi:10.1016/j.jdermsci.2004.05.004

Cited by 125 publications

(113 citation statements)

References 100 publications

(68 reference statements)

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“…It has been demonstrated that alterations in the normal distribution of keratin markers, as well as scaffold and cornified envelope markers, are excellent means of determining the integrity of the epidermal differentiation program (9,13,14,25,28,39). Therefore, immunohistochemistry analysis of early, later, and terminal differentiation markers in back skin samples from Inv-C⌬187 transgenic mice versus those of their age-matched wild-type littermates was done.…”

Section: Resultsmentioning

confidence: 99%

Role of the Cldn6 Cytoplasmic Tail Domain in Membrane Targeting and Epidermal Differentiation In Vivo

Arabzadeh¹,

Troy²,

Turksen

2006

Molecular and Cellular Biology

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It is widely recognized that the claudin (Cldn) family of four tetraspan transmembrane proteins is crucial for tight junction assembly and permeability barrier function; however, the precise role of the tail and loop domains in Cldn function is not understood. We hypothesized that the cytoplasmic tail domain of Cldn6 is crucial for membrane targeting and hence epidermal permeability barrier (EPB) formation. To test this hypothesis via a structure-function approach, we generated a tail deletion of Cldn6 (C⌬187) and evaluated its role in epidermal differentiation and EPB formation through its forced expression via the involucrin (Inv) promoter in the suprabasal compartment of the transgenic mouse epidermis. Even though a functional barrier formed, Inv-C⌬187 mice displayed histological and biochemical abnormalities in the epidermal differentiation program and stimulation of epidermal cell proliferation in both the basal and suprabasal compartments of the interfolliclar epidermis, leading to a thickening of the epidermis after 1 week of age that persisted throughout life. Although some membrane localization was evident, our studies also revealed a significant amount of not only Cldn6 but also Cldn10, Cldn11, and Cldn18 in the cytoplasm of transgenic epidermal cells as well as the activation of a protein-unfolding pathway. These findings demonstrate that the overexpression of a tail truncation mutant of Cldn6 mislocalizes Cldn6 and other Cldn proteins to the cytoplasm and triggers a postnatal increase in proliferation and aberrant differentiation of the epidermis, emphasizing the importance of the Cldn tail domain in membrane targeting and function in vivo.Claudins (Cldns) comprise a family of integral membrane proteins involved in the formation of tight junction (TJ) fibrils, which are responsible for the formation and maintenance of the epidermal permeability barrier (EPB) (36,38,40,42). Recent studies indicate that Cldn6 overexpression (34, 40) and Cldn1 deletion mutants (15) are associated with EPB defects in vivo and that the level of Cldn expression appears to be crucial for EPB integrity and function (34,38,40). Knowledge of the overall structure-function of the Cldn family of proteins is limited; however, they are known to have three distinct and characteristic functional domains: (i) four transmembranespanning regions, (ii) two extracellular loops responsible for permeability barrier formation within the paracellular space and specific ion selectivity residing within the first external loop (8,43,44), and (iii) a cytoplasmic C terminus that functions to anchor to the cytoskeleton, apparently through scaffolding molecules such as zonula occludens 1 (ZO-1) (12,22,36,38,42,43). It has been demonstrated that PDZ-binding sequences at the C terminus of the Cldn cytoplasmic tail are responsible for their association with other PDZ domain proteins (16,19,22). However, although predicted to be important, the role of the tail domain in the targeting of Cldn proteins to the membrane as well as the regulation of their f...

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Section: Resultsmentioning

confidence: 99%

Role of the Cldn6 Cytoplasmic Tail Domain in Membrane Targeting and Epidermal Differentiation In Vivo

Arabzadeh¹,

Troy²,

Turksen

2006

Molecular and Cellular Biology

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“…11 The reported values are normalized. The sampling period ranged from 5 min to 1 h. 12 The data reported correspond to loosebox experiments performed at UK Institute of Animal Health and assume similar aerosol loss rates. Additional data are available for a small (610 l) sampling chamber.…”

Section: Discussionmentioning

confidence: 99%

“…In adult humans (the most studied species with respect to airborne skin cell emissions), healthy skin typically sheds one cell layer per day. Exfoliated skin cells are typically shed as individual hexagonal plates, 25 mm on a side and 0.1-0.5 mm thick [11,12]. Mature skin cells (corneocytes) can become airborne by air moving across the skin surface [23] (see also electronic supplementary material, Particle Suspension Mechanisms); however, emissions over a short period of time can significantly increase with mechanical abrasion (e.g.…”

Section: Estimating the Shedding Rate Of Foot And Mouth Disease Virusmentioning

confidence: 99%

“…the average emission rate per animal per 24 h period 11 for the day of maximum emissions). 12 The total amount of FMDV collected by the air sampler was converted into a 24 h emission rate using equation …”

Section: Providing Context To the Hypothesized Foot And Mouth Diseasementioning

confidence: 99%

“…Mammalian skin actively sheds a significant number of skin cells (10 6 to 10 8 per day) into the environment [10][11][12] and skin cells have been observed to comprise a significant fraction (1-10%) of measured indoor and outdoor 2 aerosols and indoor dust [13][14][15][16]. Bacteria, yeast, fungi and viruses are present on the surface of skin cells (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Skin as a potential source of infectious foot and mouth disease aerosols

Dillon

2011

Proc. R. Soc. B.

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This review examines whether exfoliated, virus-infected animal skin cells could be an important source of infectious foot and mouth disease virus (FMDV) aerosols. Infectious material rafting on skin cell aerosols is an established means of transmitting other diseases. The evidence for a similar mechanism for FMDV is: (i) FMDV is trophic for animal skin and FMDV epidermis titres are high, even in macroscopically normal skin; (ii) estimates for FMDV skin cell aerosol emissions appear consistent with measured aerosol emission rates and are orders of magnitude larger than the minimum infectious dose; (iii) the timing of infectious FMDV aerosol emissions is consistent with the timing of high FMDV skin concentrations; (iv) measured FMDV aerosol sizes are consistent with skin cell aerosols; and (v) FMDV stability in natural aerosols is consistent with that expected for skin cell aerosols. While these findings support the hypothesis, this review is insufficient, in and of itself, to prove the hypothesis and specific follow-on experiments are proposed. If this hypothesis is validated, (i) new FMDV detection, management and decontamination approaches could be developed and (ii) the relevance of skin cells to the spread of viral disease may need to be reassessed as skin cells may protect viruses against otherwise adverse environmental conditions.

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Oral Epithelium

Squier¹,

Brogden²

2011

Human Oral Mucosa

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Epidermal desquamation

Cited by 125 publications

References 100 publications

Role of the Cldn6 Cytoplasmic Tail Domain in Membrane Targeting and Epidermal Differentiation In Vivo

Role of the Cldn6 Cytoplasmic Tail Domain in Membrane Targeting and Epidermal Differentiation In Vivo

Skin as a potential source of infectious foot and mouth disease aerosols

Oral Epithelium

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