involucrin and Skin-Diseases

In the meta-analysis of public microarray databases for different skin diseases, we revealed seven commonly up-regulated genes, DSG3, KRT6, MAP17, PLSCR1, RPM2, SOD2 and SPRR2B. We postulated that the genes selected from the meta-analysis may be potentially associated with the abnormal keratinocyte differentiation. To demonstrate this postulation, we alternatively evaluated whether the genes of interest in the meta-analysis can be regulated by T-helper (Th) cell cytokines in normal human epidermal keratinocytes (NHEK). We found that MAP17 was significantly up-regulated in response to interferon-gamma, interleukin 4 (IL-4), IL-6, IL-17A or IL-22 in NHEK. Interestingly, MAP17 was originally reported to interact with PDZK1; in turn, the PDZK1 gene is localized within the atopic dermatitis-linked region on human chromosome 1q21. In an attempt to evaluate whether MAP17 regulates the expression of cornified envelope-associated genes at the 1q21 locus, such as filaggrin, loricrin and involucrin, we found that the over-expression of MAP17 in HaCaT keratinocytes significantly decreased the expression of filaggrin. Taken together, the Th cell cytokine-induced up-regulation of MAP17 expression may be linked to the down-regulation of filaggrin in NHEK, which may be associated with the abnormal epidermal differentiation observed in the dermatological diseases.

Topics: Cell Differentiation; Cell Line, Transformed; Cells, Cultured; Computational Biology; Cytokines; Databases, Genetic; Desmoglein 3; Down-Regulation; Filaggrin Proteins; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Humans; Interferon-gamma; Interleukin-17; Interleukin-22; Interleukin-4; Interleukins; Intermediate Filament Proteins; Keratin-10; Keratin-6; Keratinocytes; Membrane Proteins; Phospholipid Transfer Proteins; Protein Precursors; Skin Diseases; Superoxide Dismutase; T-Lymphocytes, Helper-Inducer; Transcription, Genetic; Transfection; Transglutaminases; Up-Regulation

This review summarizes recent data on the keratinocyte, the major cell type in the epidermis. A two-state model is proposed: in the "resting" state, the keratinocyte is committed to a program of terminal differentiation focusing on production of an efficient barrier, the stratum corneum, and of the epidermal basement membrane; the activated state, first discovered in cell culture studies, occurs in vivo during epidermal wound healing and inflammatory skin diseases.

Topics: Cell Differentiation; Epidermal Cells; Epidermis; Filaggrin Proteins; Humans; Interleukin-1; Intermediate Filament Proteins; Keratinocytes; Keratins; Protein Precursors; Skin Diseases; Transglutaminases; Wound Healing

Chronic wounds remain a major unmet healthcare challenge, associated with substantial morbidity and economic costs. Therefore, novel treatment strategies and therapeutic approaches need to be urgently developed. Yet, despite the increasingly recognized importance of neurohormonal signaling in skin physiology, the neuroendocrine regulation of cutaneous wound healing has received surprisingly little attention. Human skin, and its appendages, locally express the pleiotropic neurohormone prolactin (PRL), which not only regulates lactation but also hair follicle cycling, angiogenesis, keratinocyte proliferation, and epithelial stem cell functions. Therefore, we examined the effects of PRL in experimentally wounded female human skin organ culture. Overall, this revealed that PRL slightly, but significantly, inhibited epidermal regeneration (reepithelialisation), cytokeratin 6 protein expression and intraepidermal mitochondrial activity (MTCO1 expression), while it promoted keratinocyte terminal differentiation (i.e. involucrin expression) ex vivo. If the current pilot data are confirmed by further studies, PRL may serve as one of the-rarely studied-negative regulators of cutaneous wound healing that control excessive reepithelialisation. This raises the intriguing and clinically relevant question of whether PRL receptor antagonists could actually promote epidermal repair after human skin wounding.

Topics: Electron Transport Complex IV; Energy Metabolism; Female; Humans; Keratin-6; Keratinocytes; Mitochondria; Organ Culture Techniques; Prolactin; Protein Precursors; Receptors, Prolactin; Regeneration; Skin; Skin Diseases; Wound Healing

In this manuscript, we report observations of the effects of rapamycin in an organotypic culture of human skin explants. The tissues were cultured for 5 days at the air-liquid interface or in submersed conditions with media with and without rapamycin at 2 nM concentration. Histological analysis of tissue sections indicated that rapamycin-treated samples maintained a better epidermal structure in the upper layers of the tissue than untreated samples, mostly evident when skin was cultured in submersed conditions. A significant decrease in the number of positive proliferative cells using the Ki67 antigen was observed when specimens were treated with rapamycin, in both air-liquid and submersed conditions but apoptosis differences between treated and untreated specimens, as seen by cleaved caspase-3 positive cells, were only observed in submersed specimens. Finally, a decrease and variability in the location in the expression of the differentiation marker involucrin and in E-cadherin were also evident in submersed samples. These results suggest that the development of topical applications containing rapamycin, instead of systemic delivery, may be a useful tool in the treatment of skin diseases that require reduction of proliferation and modulation or control of keratinocyte differentiation.

Topics: Administration, Topical; Apoptosis; Cadherins; Caspase 3; Cell Differentiation; Cell Proliferation; Humans; Keratinocytes; Ki-67 Antigen; Organ Culture Techniques; Protein Precursors; Sirolimus; Skin; Skin Diseases; Skin Transplantation; Tissue Engineering

Acral peeling skin syndrome (APSS) is an autosomal recessive skin disorder characterized by acral blistering and peeling of the outermost layers of the epidermis. It is caused by mutations in the gene for transglutaminase 5, TGM5. Here, we report on clinical and molecular findings in 11 patients and extend the TGM5 mutation database by four, to our knowledge, previously unreported mutations: p.M1T, p.L41P, p.L214CfsX15, and p.S604IfsX9. The recurrent mutation p.G113C was found in 9 patients, but also in 3 of 100 control individuals in a heterozygous state, indicating that APSS might be more widespread than hitherto expected. Using quantitative real-time PCR, immunoblotting, and immunofluorescence analysis, we demonstrate that expression and distribution of several epidermal differentiation markers and corneodesmosin (CDSN) is altered in APSS keratinocytes and skin. Although the expression of transglutaminases 1 and 3 was not changed, we found an upregulation of keratin 1, keratin 10, involucrin, loricrin, and CDSN, probably as compensatory mechanisms for stabilization of the epidermal barrier. Our results give insights into the consequences of TGM5 mutations on terminal epidermal differentiation.

Topics: Adult; Biopsy; Case-Control Studies; Cell Differentiation; Cells, Cultured; Child; Child, Preschool; Dermatitis, Exfoliative; Epidermis; Glycoproteins; Humans; Infant; Intercellular Signaling Peptides and Proteins; Keratin-1; Keratin-10; Keratinocytes; Mutation; Pigmentation Disorders; Protein Precursors; Skin Diseases; Transglutaminases

Epidermodysplasia verruciformis (EV) is a rare genodermatosis with susceptibility to human papillomavirus (HPV) infection, and high risk of skin cancer considered a model of viral oncogenesis.. Fifteen cases of EV plane wart (PW)-type lesions (EV) and 14 cases of PW in healthy individuals were subjected to immunohistochemical technique for cytokeratins (K) 1, 10, 14, 16, 4, involucrin, filaggrin and e-cadherin.. K1/10 showed retarded or negative expression in EV, being substituted by K14. Expression of K14 occurred in the basal and suprabasal layers in both groups, but in EV, its expression was observed up to the more superficial layers. Both groups showed positivity for K16 and K4, involucrin expression in lower levels of the spinous layer and unaltered filaggrin expression. E-cadherin expression was diminished at the koilocytotic foci of both lesions, more superficially in EV.. Infection by HPV may alter the differentiation status of the epidermis, leading to a major expression of K14, delayed or absent expression of K1/10 and earlier involucrin expression, especially in EV. It also stimulates the expression of K16 and K4. Filaggrin expression is not altered, and e-cadherin is diminished in superficial koilocytotic cells' foci in EV.

Topics: Adult; Cadherins; Epidermodysplasia Verruciformis; Female; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Papillomavirus Infections; Protein Precursors; Skin Diseases

Inflammatory skin disorders result in significant epidermal changes, including keratinocyte hyperproliferation, incomplete differentiation, and impaired barrier. Here we test whether, conversely, an impaired epidermal barrier can promote an inflammatory response. Mice lacking the transcription factor Kruppel-like factor 4 (Klf4) have a severe defect in epidermal barrier acquisition. Transcription profiling of Klf4(-/-) newborn skin revealed similar changes in gene expression to involved psoriatic plaques, including a significant upregulation of the gap junction protein connexin 26 (Cx26). Ectopic expression of Cx26 from the epidermis-specific involucrin (INV) promoter (INV-Cx26) demonstrated that downregulation of Cx26 is required for barrier acquisition during development. In juvenile and adult mice, persistent Cx26 expression kept wounded epidermis in a hyperproliferative state, blocked the transition to remodeling, and led to an infiltration of immune cells. Mechanistically, ectopic expression of Cx26 in keratinocytes resulted in increased ATP release, which delayed epidermal barrier recovery and promoted an inflammatory response in resident immune cells. These results provide a molecular link between barrier acquisition in utero and epidermal remodeling after wounding. More generally, these studies suggest that the most effective treatments for inflammatory skin disorders might concomitantly suppress the immune response and enhance epidermal differentiation to restore the barrier.

Topics: Animals; Animals, Newborn; Connexin 26; Connexins; Epidermis; Gene Expression Regulation, Developmental; Inflammation; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Mice; Mice, Transgenic; Promoter Regions, Genetic; Protein Precursors; Skin Diseases; Wound Healing

Cutaneous xerosis is a common clinical condition associated with an altered barrier function of the stratum corneum. Xerotic skin appears dry, rough and slightly scaling. Patients complain of pruritus and stinging. Our aim was to investigate the clinical effects of a cosmetic ointment (Scherilan) in patients with circumscribed senile xerosis (also called asteatotic eczema). Moreover, variations in expression of epidermal proteins such as keratin (K)-5 and involucrin, detected by immunohistochemistry, were also evaluated before and after topical treatment. We enrolled 30 patients (11 males, 19 females) with asteatotic eczema. We examined dryness, roughness and desquamation and symptoms such as itching and dryness. A score of 0 to 3 was assigned to each of these parameters. A biopsy was performed in seven patients before and after a 21-day topical treatment. All skin specimens were then immunostained with antibodies to K5 and involucrin. At day 7 or 21 of treatment all signs of xerosis and pruritus were significantly reduced; furthermore, the reduction increased with the duration of therapy. Before treatment K5 was strongly expressed in stratum basale (SB) and stratum spinosum (SS), while involucrin was strongly expressed in stratum granulosum (SG) and the upper portion of SS. In contrast, after treatment immunostaining for K5 was restricted to SB and the lower part of SS, while involucrin showed intense staining in SG. We highlight the importance of treating cutaneous xerosis with an ointment such as this one, which probably induces an increase of lipid content of the SC intercellular matrix.

Topics: Aged; Biopsy; Cell Proliferation; Cosmetics; Eczema; Epidermis; Female; Glycolates; Humans; Immunohistochemistry; Keratin-5; Keratins; Lipid Metabolism; Lipids; Male; Middle Aged; Ointments; Protein Precursors; Pruritus; Skin Diseases; Time Factors; Treatment Outcome; Vitamin E

Topics: Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Proteins; Middle Aged; Protein Precursors; Sjogren's Syndrome; Skin Diseases

Solanum glaucophyllum (Sg) (synonym S. malacoxylon) is a plant toxic to cattle due to its high levels of 1,25-dihydroxyvitamin D3 as glycoside derivatives. Sg causes a disease characterized by wasting and calcification of soft tissues. The effects of vitamin D are not only important in calcium homeostasis, but also in immune regulation, cell growth and cell differentiation. Skin samples in Sg-intoxicated and control heifers were studied histologically. Cellular differentiation and proliferation were analysed by immunohistochemical expression of cytokeratins, involucrin and proliferating cell nuclear antigen (PCNA). The results were obtained by image processing and analysis and were statistically evaluated. Sg-intoxicated cattle showed atrophy of epidermis and severe involution of hair follicles and of sebaceous and sweat glands. As judged by PCNA expression, cellular proliferation was reduced, even though the reduction was not statistically significant. The analysed markers of differentiation, e.g. involucrin and cytokeratins 10 and 11, changed in relation to Sg-poisoning. The possible pathogenesis of the skin lesions is discussed.

Topics: Animals; Antibodies, Monoclonal; Argentina; Body Weight; Cattle; Cattle Diseases; Cell Differentiation; Cell Division; Female; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Plant Poisoning; Proliferating Cell Nuclear Antigen; Protein Precursors; Skin Diseases; Solanaceae; Solanaceous Alkaloids; Vitamin D

Severe xerosis occurs in approximately 20% of human immunodeficiency virus seropositive patients. Changes in cutaneous innervation have been found in various inflammatory skin diseases and in xerotic skin in familial amyloid. We have therefore carried out a quantitative examination of the cutaneous peptidergic innervation in human immunodeficiency virus-associated xerosis. Immunohistochemistry and image analysis quantitation were used to compare total cutaneous innervation (protein gene product 9.5), calcitonin gene-related peptide, substance P, and vasoactive intestinal peptide peptidergic fibers, at two sites in the skin of human immunodeficiency virus-associated xerosis patients (upper arm, n = 12; upper leg, n = 11) and site-matched seronegative controls (upper arm, n = 10; upper leg, n = 10). Measurement of lengths of fibers of each type was carried out for each subject in the epidermis and papillary dermis, and around the sweat glands. Immunostained mast cells in these areas were counted. Epidermal integrity and maturation were assessed by immunostaining for involucrin. There were significant (Mann-Whitney U test; p < 0.02) decreases in total lengths of protein gene product 9.5 fibers in both epidermis/papillary dermis and sweat gland fields; of calcitonin gene-related peptide innervation in the epidermis/papillary dermis; and of substance P innervation of the sweat glands. There were no differences in the distribution of mast cells, or in the epidermal expression of involucrin. Depletion of the calcitonin gene-related peptide innervation may affect the nutrient blood supply of the upper dermis, and the integrity and function of basal epidermis and Langerhans cells. Diminished substance P innervation of the sweat glands may affect their secretory activity. Both of these changes may be implicated in the development of xerosis.

Topics: Adult; Aging; Anti-HIV Agents; Calcitonin Gene-Related Peptide; Disease Progression; Female; HIV Infections; Humans; Male; Middle Aged; Nervous System Physiological Phenomena; Peptides; Protein Precursors; Skin; Skin Diseases; Substance P; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

To investigate the function of trichohyalin during terminal differentiation of the skin, immunohistochemical studies were performed on trichohyalin and its related proteins, filaggrin and involucrin, the components of the cornified cell envelope. In skin disorders unrelated to tumours, weak trichohyalin expression was found in a few granular cells or in the horny layer of psoriasis, ichthyosis, keratosis pilaris, porokeratosis, chronic dermatitis and callus. Similar trichohyalin expression was found in epidermal tumours, such as seborrheic keratosis, actinic keratosis, Bowen's disease and well-differentiated squamous cell carcinoma. In follicular tumours, trichohyalin expression was positive in trichoepithelioma, keratotic basal cell epithelioma, proliferating trichilemmal tumour, trichilemmoma, pilomatricoma and keratoacanthoma. From comparative studies with filaggrin and involucrin, trichohyalin expression was co-localized with them in molluscum contagiosum, keratoacanthoma and pilomatricoma. From this study, trichohyalin is revealed to have close functional relationship with other markers of terminal differentiation as a precursor of the cornified cell envelope of the skin.

Topics: Animals; Antigens, Differentiation; Case-Control Studies; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Protein Precursors; Rabbits; Skin Diseases

The hallmarks of dry skin (xerosis) are scaliness and loss of elasticity. Decreased hydration and a disturbed lipid content of the stratum corneum are also well-known features. The frequency of dry skin increases with ageing. The aim of this study was to examine if these known features of dry skin are related to changes in epidermal proliferation and differentiation. In addition, age-related changes in normal and in dry skin were examined: 62 volunteers were divided by clinical grading and biophysical measurements into groups with young/normal, young/dry, aged/normal and aged/dry skin. Biopsy samples from the lower legs (most severe dryness) were examined by two-dimensional gel electrophoresis and by immunohistochemistry for epidermal proliferation, epidermal keratins and cornified envelope proteins. There was a slight increase in proliferation in both groups with dry skin compared with normal skin of the corresponding age. In aged/normal compared with young/normal skin there was a significant decrease in proliferation. However, epidermal proliferation was the same in aged/dry skin as in young/normal skin. For epidermal differentiation, an age-independent decrease of keratins K1 and K10 and an associated increase in the basal keratins K5 and K14 was detected in dry skin. There was also an age-independent premature expression of the cornified envelope protein involucrin. In contrast, loricrin expression was not influenced by dry skin conditions. In summary, epidermal proliferation was significantly decreased in aged/normal compared with young/normal skin. Dry skin showed significant changes in the epidermal expression of basal and differentiation-related keratins, and a premature expression of involucrin irrespective of age.

Topics: Adult; Aged; Aging; Body Water; Cell Differentiation; Cell Division; Electrophoresis, Gel, Two-Dimensional; Epidermis; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Protein Precursors; Skin Diseases; Water Loss, Insensible

Loricrin is a glycine-, serine-, and cysteine-rich protein expressed very late in epidermal differentiation in the granular layers of normal human epidermis. Subsequently, loricrin becomes cross-linked by the activity of transglutaminases TGK/E as a major component of the cornified cell envelope by N epsilon-(gamma-glutamyl)lysine isopeptide bonds. In this study, 115 biopsy specimens from patients with various cutaneous diseases with a morphologically altered epidermal differentiation were analyzed with use of immunohistology with antibodies to loricrin and to involucrin. In addition, antibodies to filaggrin were used for ichthyotic lesions. In contrast to involucrin, loricrin expression was consistently down-regulated in agranulotic, parakeratotic keratinization as observed in psoriasis, dermatitis, pityriasis lichenoides, porokeratosis, or precancerous and malignant squamous lesions. High levels of loricrin were found in hypergranulotic and hyperorthokeratotic epidermis as observed in lichen planus, benign papillomas, and pseudocarcinomatous hyperplasia. Eleven biopsy specimens from patients with ichthyosis vulgaris showed a normal staining in the granular layers. Our results demonstrate that loricrin expression is closely linked to an orthokeratotic phenotype of human epidermal keratinization. The different expression patterns of loricrin and involucrin provide further evidence that these proteins are regulated by different mechanisms and serve different functions during terminal epidermal differentiation.

Topics: Filaggrin Proteins; Humans; Ichthyosis; Immunohistochemistry; Intermediate Filament Proteins; Membrane Proteins; Protein Precursors; Skin; Skin Diseases; Skin Neoplasms

Topics: Cell Differentiation; Epidermal Cells; Epidermis; Humans; Keratins; Protein Precursors; Skin Diseases

The expression of involucrin was examined in 23 skin tumours of hair follicle origin, 17 tumours of sweat gland origin and three tumours of unknown origin, using an immunoperoxidase technique. All tumours from the hair follicle showed a positive reaction for involucrin. In particular keratoacanthoma and the squamous eddies in various tumours stained strongly. Trichofolliculoma, trichilemmoma and pilomatrixoma exhibited characteristic staining patterns which resembled those in the normal hair follicle. On the other hand the majority of the tumours of sweat gland origin did not stain, with restricted positive reactions in areas showing lumen formation or squamous metaplasia. In contrast to the lack of staining in syringoma, a positive reaction was observed in desmoplastic trichoepithelioma, which is histologically similar to syringoma. Clear cell acanthoma, the origin of which is still controversial, showed a staining pattern which indicated that its origin may not be in the sweat gland. These results suggest that testing for involucrin in skin appendage tumours may be very useful for understanding the kinetics of maturation as well as in determining the origin of the tumours.

Topics: Carcinoma, Squamous Cell; Cystadenoma; Hair; Hair Diseases; Humans; Immunoenzyme Techniques; Keratoacanthoma; Protein Precursors; Skin Diseases; Skin Neoplasms; Sweat Gland Neoplasms; Sweat Glands

Fifteen keratoacanthomas and fifteen squamous cell carcinomas of the skin were examined by immunoperoxidase methods for involucrin and both 45- and 63-kilodalton keratins. Keratoacanthomas showed a relatively homogeneous staining pattern for involucrin; all cells except basal cells stained with mild to moderate intensity. Squamous cell carcinomas disclosed a highly irregular involucrin staining pattern with marked variation in staining intensity from cell to cell. Staining patterns for keratin proteins did not appear to distinguish between keratoacanthomas and squamous cell carcinomas. The 45-kilodalton keratin pattern showed diffuse staining within both keratoacanthomas and squamous cell carcinomas, and the 63-kilodalton keratin pattern consisted of focal staining, mostly of dyskeratotic cells. These results suggest that involucrin may serve as a diagnostic aid in differentiating between squamous cell carcinomas and keratoacanthomas. In addition, other lesions in the differential diagnosis of keratoacanthoma and squamous cell carcinoma were also examined for involucrin.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Epidermis; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Keratoacanthoma; Middle Aged; Neoplasm Proteins; Protein Precursors; Sebaceous Glands; Skin Diseases; Skin Neoplasms; Sweat Glands

Involucrin has been recognized recently as a marker of terminal differentiation of squamous epithelial cells and also as a useful marker for keratinization; its expression in epithelial tumors of oral and pharyngeal mucosa and skin was examined. Involucrin in normal oral mucosa and skin was restricted to the granular and upper spinous layers and was absent in the basal layer. Hyperkeratosis was characterized by strong positive staining for involucrum in spinous and granular cell layers. A similar pattern was noted in seborrheic keratosis and verruca vulgaris. Condyloma acuminatum specimens revealed slight staining, whereas Paget cells were negative. Calcifying epitheliomas of Malherbe were usually unreactive. Papillomas exhibited the regular distribution of involucrin, as found in normal squamous epithelium. Basal cell carcinomas were generally negative, whereas squamous cell carcinomas showed an irregular distribution of involucrin. Immunohistochemical staining for involucrin may be useful for identification of keratinizing cells in epithelial tumor foci, just as is the use of monoclonal antibody to keratin KL1.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Papilloma; Pharyngeal Neoplasms; Protein Precursors; Skin Diseases; Skin Neoplasms; Staining and Labeling

The expression of involucrin was studied in a group of skin neoplasms, mostly of adnexal origin. As happens with other types of epithelial tumours, involucrin was detected in the most differentiated areas (presenting a squamoid or ductal differentiation). No reactivity was observed in non-epithelial skin tumours. These results suggest that involucrin is a specific marker for epithelial and adnexal differentiation of skin tumours and may thus be a useful aid in histopathologic diagnosis and classification of neoplasms.

Topics: Carcinoma; Cell Differentiation; Histocytochemistry; Humans; Immunoenzyme Techniques; Protein Precursors; Retrospective Studies; Skin; Skin Diseases; Skin Neoplasms

Involucrin is a recently recognized structural component of mature squamous epithelial cells. We examined involucrin expression using an immunoperoxidase technique in normal skin and in a variety of epidermal hyperplasias and neoplasms to determine whether distinctive staining patterns existed within these lesions. Four patterns of reactivity were observed: diffuse intracellular staining typical of keratinocytes of the upper third of normal epidermis and epidermal hyperplasias and benign neoplasms; staining at cell borders, seen principally in benign epidermal neoplasms; patchy staining characteristic of squamous cell carcinoma in situ; and absence of staining in benign and neoplastic basaloid epithelium. Invasive nests of squamous cell carcinomas were negative for involucrin reactivity, whereas pseudoinvasive tongues of epithelium at the bases of keratoacanthomas were focally positive. These results suggest that immunoperoxidase staining for involucrin may be useful in distinguishing certain benign from malignant epidermal neoplasms as well as in understanding the altered maturation and kinetics of proliferative processes afflicting keratinocytes.

Topics: Cell Differentiation; Cell Transformation, Neoplastic; Epidermal Cells; Epidermis; Histocytochemistry; Humans; Immunoenzyme Techniques; Protein Precursors; Skin Diseases; Skin Neoplasms

Based on recent morphologic, histochemical, and biochemical data, we propose a heterogeneous two-compartment model of the stratum corneum that ascribes a special role for intercellular lipids in the regulation of stratum corneum barrier function and desquamation. The evidence in favor of the model and several predictions based on the model are surveyed in this review.

Topics: Ceramides; Fatty Acids, Nonesterified; Histocytochemistry; Humans; Keratins; Lipid Metabolism; Lipids; Protein Precursors; Skin; Skin Diseases; Staining and Labeling; Sterols; Steryl-Sulfatase; Sulfatases