Trends in Electron Microscopy of Skin

Wolff, Klaus; Wolff-Schreiner, Elisabeth C.

doi:10.1111/1523-1747.ep12512480

Cited by 39 publications

(8 citation statements)

References 136 publications

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“…Pemphigus is an autoimmune blistering disease altering intercellular adhesion in the stratified squamous epithelium in which patients develop extensive blisters reminiscent of severe burns. In the epidermis, α9 is one of the most abundant AChR subtypes, being expressed predominantly by suprabasal (prickle) KCs [13,28] that are believed to be the most mobile cells, since they have to constantly assemble and disassemble their adherens and desmosomal junctions to allow for upward migration through the epidermal layers [29].…”

Section: Discussionmentioning

confidence: 99%

Central role of α9 acetylcholine receptor in coordinating keratinocyte adhesion and motility at the initiation of epithelialization

Chernyavsky¹,

Arredondo²,

Vetter³

et al. 2007

Experimental Cell Research

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Epithelialization, a major component of wound healing, depends on keratinocyte adhesion and migration. Initiation of migration relies upon the ability of keratinocytes to free themselves from neighboring cells and basement membrane. The local cytotransmitter acetylcholine (ACh) controls keratinocyte adhesion and locomotion through different classes of ACh receptors (AChR). In this study, we explored signaling pathways downstream of the alpha9 AChR subtype that had been shown to control cell shape and cytoplasm mobility. Inactivation of alpha9 signaling by pharmacologic antagonism and RNA interference in keratinocyte cultures and null mutation in knockout mice delayed wound re-epithelialization in vitro and in vivo, respectively, and diminished the extent of colony scattering and cell outgrowth from the megacolony. Although keratinocytes at the leading edge elongated, produced filopodia and moved out, most of them remained anchored to the substrate by long cytoplasmic processes that stretched during their migration instead of retracting the uropod. Since the velocity of keratinocyte migration was not altered, we investigated the role of alpha9 in assembly/disassembly of the cell-cell and cell-matrix adhesion complexes. Stimulation of alpha9 upregulated in a time-dependent fashion phosphorylation of the adhesion molecules comprising focal adhesions (FAK, paxillin) and intercellular junctions (beta-catenin, desmoglein 3) as well as cytokeratins. Stimulation of alpha9 was associated with activation of phospholipase C, Src, EGF receptor kinase, protein kinase C, Rac and Rho, whereas inhibition of this receptor interfered with phosphorylation of adhesion and cytoskeletal proteins, and also altered cell-cell cohesion. We conclude that signaling through alpha9 AChR is critical for completion of the very early stages of epithelialization. By activating alpha9 AChR, ACh can control the dynamics and strength of cell-cell cohesion, disabling of a trailing uropod and disassembly and reassembly of focal adhesions, thus facilitating crawling locomotion.

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Section: Discussionmentioning

confidence: 99%

Central role of α9 acetylcholine receptor in coordinating keratinocyte adhesion and motility at the initiation of epithelialization

Chernyavsky¹,

Arredondo²,

Vetter³

et al. 2007

Experimental Cell Research

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“…This detail accounts for the fact that the clinical lesions are hypopigmented and not achromic. The content of melanin granules in the melanocytes is transferred to the surrounding keratinocytes through a process of phagocytosis, and later on they are broken down when they reach the surface (2), since there are various enzymes to process them (3). The mechanisms through which the granules of the melanosomes and their dendrites are transferred to the keratinocytes are complex, there being multiple genetic and biochemical factors for both cells (4–8).…”

Section: Discussionmentioning

confidence: 99%

Cole Disease: Hypopigmentation with Punctate Keratosis of the Palms and Soles

Vignale

Yusín

Panuncio

et al. 2002

Pediatric Dermatology

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Cole disease is an uncommon disorder characterized by distinctive cutaneous hypopigmentation and punctate keratosis of the palms and soles. It is a congenital skin disease with an autosomal dominant inheritance pattern. We report two patients from a family with 15 members, 5 of whom were affected. One of the patients had both types of lesions since birth, while in the other they arose in the first months of life. We studied the pedigree, histopathology, immunohistochemistry, and electron microscopy findings of the hypopigmented macules with the patients' normal skin used as a control. The pedigree showed involvement of both genders, with a Mendelian autosomal dominant inheritance pattern with phenotypic variability in the family. Immunohistochemistry showed a reduction in the melanin pigment in the keratinocytes and normal pigmentation in the melanocytes. Ultrastructural studies showed a strong contrast between the large number of melanosomes in the body and dendrites of the melanocytes, in contrast with the small number of these organelles in the neighboring keratinocytes. These findings suggest that this disease is a primary congenital disorder of the transfer mechanisms of the melanosomes from melanocytes to keratinocytes in hypopigmented lesions, associated with abnormal epidermopoiesis in the punctate hyperkeratosis.

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“…The physiologic function and the target protease of bikunin in the epidermis remain unknown at present. The major adhesion structure of keratinocytes, the desmosome, physiologically dissociates during cell division of keratinocytes in epidermis (Wolf and Wolf-Schreiner, 1976;Koch et al, 1990;Buxton et al, 1993), and the mechanism of this desmosomal dissociation during cell division remains unknown. It may be the role of bikunin to regulate dissociation of desmosomes of keratinocytes during cell division by inhibition of protease activity.…”

Section: Discussionmentioning

confidence: 99%

“…In human epidermis, keratinocytes are bound to each other by desmosomes, the adhesion and dissociation of which occurs repeatedly during mitosis and differentiation (Wolf and Wolf-Schreiner, 1976;Jones et al, 1986;Kitajima et al, 1986Kitajima et al, , 1987Koch et al, 1990;Buxton et al, 1993). Although it is considered that desmosomes are digested by proteases like plasmin during keratinocyte dissociation (Hennings et al, 1980(Hennings et al, , 1983Boyce and Ham, 1983), the mechanisms of inhibition of plasmin or other proteases are not completely understood and the mechanisms of dissociation under normal conditions have not been completely clarified yet.…”

mentioning

confidence: 99%

Bikunin, a Serine Protease Inhibitor, is Present on the Cell Boundary of Epidermis

Cui

Aragane

Maeda

et al. 1999

Journal of Investigative Dermatology

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Bikunin, which is an inhibitor of serine proteases, is widely distributed in human tissues, including liver, kidney, and mucous membranes of the stomach and colon. The aim of this study was to clarify whether bikunin is expressed in human epidermis and its appendages. Immunoblot analysis using a specific polyclonal antibody to bikunin revealed that a single 43 kDa protein is present in the cell lysate from the human keratinocyte cell line HaCaT. Immunohistochemically, dotted reaction products stained with anti-bikunin antibody were localized on the cell boundary in both basal and spinous cell layers, except on the cell boundary of the basal cells facing the basal membrane. There were no reaction products in the granular-horny cell layers. Reaction products stained with anti-bikunin antibody were also observed on the hair bulb cells and eccrine sweat gland cells, but not on apocrine sweat glands. Also, reaction products were observed on the luminal surface of the renal proximal tubules and in the cytoplasm of these cells. In immunoelectron microscopy, gold particles were observed on the cell membranes close to the desmosomal structures. Reverse transcription-polymerase chain reaction and northern blot analyses showed that mRNA specific for bikunin was expressed in HaCaT cells and human epidermal keratinocytes obtained from suction blisters, and was contained in a commercially available human keratinocyte cDNA preparation. These findings indicate that bikunin is expressed in keratinocytes and may play an important part in regulating keratinocytes in either mitosis or inflammation.

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Trends in Electron Microscopy of Skin

Cited by 39 publications

References 136 publications

Central role of α9 acetylcholine receptor in coordinating keratinocyte adhesion and motility at the initiation of epithelialization

Central role of α9 acetylcholine receptor in coordinating keratinocyte adhesion and motility at the initiation of epithelialization

Cole Disease: Hypopigmentation with Punctate Keratosis of the Palms and Soles

Bikunin, a Serine Protease Inhibitor, is Present on the Cell Boundary of Epidermis

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