Epidermal hyperplasia

Kang S, Duell EA, Fisher GJ, et al (1995) Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol 105 549-556... 

In addition, the ductal mucosa in the caudal region was hyperplastic, being lined by 4-5 rows of cells. Epidermal hyperplasia following topical application of 8-D on rabbit s ear is known (19). 

Black, J.J. 1983. Epidermal hyperplasia and neoplasia in brown bullheads (Ictalurus nebulosus) in response to repeated applications of a PAH containing extract of polluted river sediment. Pages 99-111 in M. Cooke and A.J. Dennis (eds.). Polynuclear Aromatic Hydrocarbons Formation, Metabolism and Measurement. Battelle Press, Columbus, OH. 

In animal studies, mirex, was tested at a dermal dose of 3.6 mg/kg 4 weeks in female CD-1 mice for tumor promoter activity and evidence of epidermal hyperplasia after initiation with 200 nmol/day 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. Positive control mice were treated with 2 nmol/day of the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), following initiation with DMBA. A third group of mice were treated with both 3.6 mg/kg mirex and 2... 

As described so far, mast cells were found to exacerbate immune reactions, including allergic responses. A recent paper shows that mast cells are also critical to limit pathology in a murine CHS model, including the reduction of infiltrating cells, epidermal hyperplasia, and necrosis... 

Mouse. A group of 20 female SEN mice, four weeks of age, was treated twice weekly for 51 weeks with 0.2 mL of a 100 mg/mL solution of benzoyl peroxide in acetone applied to the skin shaved 48 h previously. A group of 15 mice receiving 0.2 mL acetone served as controls. At the termination of the experiment, there were no skin tumours among the control mice, compared with 8/20 in the benzoyl peroxide-treated mice Ip < 0.05), of which 5/20 were squamous-cell carcinomas. The first tumour developed in week 24. Six of 20 mice showed epidermal hyperplasia (Kurokawa et al., 1984). 

Ah receptor (AHR) A protein coded for by a gene of the Ah locus. The initial location of the Ah receptor is believed to be in the cytosol and, after binding to a ligand such as TCDD, is transported to the nucleus. Binding of aromatic hydrocarbons to the Ah receptor of mice is a prerequisite for the induction of many xenobiotic metabolizing enzymes, as well as for two responses to TCDD epidermal hyperplasia and thymic atrophy. Ah-responsive mice have a high-affinity receptor, whereas the Ah-nonresponsive mice have a low-affinity receptor. 

Dermal Effects. Dermal effects of several CDD congeners have been studied in animals. Acute dermal exposure to 0.01 g (newborn) and 0.1 g 2,3,7,8-TCDD (adult) per animal caused hyperkeratosis and epidermal hyperplasia in hairless HRS/J mice (Puhvel and Sakamoto 1988). An involution of sebaceous glands was found in both (haired and hairless) strains. Similar results were found following intermediate-duration exposure (Puhvel et al. 1982). Furthermore, acne-like lesions in the ears were found in CD-I mice following exposure to 0.1 g 2,3,7,8-TCDD applied on the pre-shaved back 2 days a week for 30 weeks (Berry et al. 1978, 1979). In contrast, no dermal effects were observed in Swiss Webster mice exposed to 0.005 g 2,3,7,8-TCDD/application, 3 days a week for up to 104 weeks (NTP 1982a). 

Denda, M. Inoue, K. Fuziwara, S. Denda, S., P2K purinergic receptor antagonist accelerates skin barrier repair and prevents epidermal hyperplasia induced by skin barrier disruption. J. Invest. Dermatol. 119, 1034-1040, 2002. 

Dry, scaly skin is characterized by a decrease in the water retention capacity of the stratum corneum (SC),1 with water content diminished to less than 10%. Barrier function of the SC is usually declined, and transepidermal water loss (TEWL) is increased because of an abnormality on barrier homeostasis.2 People feel tightness of their skin, and the skin surface becomes rough, scaly, and sensitive. Hyperkeratosis, abnormal scaling, and epidermal hyperplasia are usually observed in the dry skin.2 Keratinization also shows abnormal features.2 These phenomena are commonly observed in atopic dermatitis and psoriasis.3 Dermatitis induced by environmental factors such as exposure to chemicals, low humidity, and UV radiation also shows these features. Thus, many researchers have been investigating the cause and treatment of dry skin, and there is currently great interest in adequate model systems for dry skin studies. In this chapter, I will describe several model systems of dry skin for clinical research of dermatitis associated with skin surface dryness and also mention recent studies to improve the dry skin. 

Although repeated barrier disruption induces inflammation, epidermal hyperplasia, and abnormal keratinization, there are several histological differences between this model and psoriasis. Gerritsen et al.19 reported the absence of some characteristic features of psoriasis in the dry skin induced by repeated tape stripping. They also demonstrated that filaggrin expression in the model system was different from that in psoriasis. The mechanism underlying the clonical skin diseases such as psoriasis remains to be investigated. 

The effect of a surfactant on skin depends on the type of surfactant as described earlier. Wilhelm et al. demonstrated the irritation potential of anionic surfactants.21 They evaluated the effects of sodium salts of n-alkyl sulfates with variable carbon chain length on TEWL and found that a C12 analog gave a maximum response. They suggested that the mechanisms responsible for the hydration of SC are related to the irritation properties of the surfactants. Leveque et al. also suggested22 that the hyperhydration of SC is consecutive to the inflammation process. They demonstrated that the increase of TEWL was induced by SDS without removal of SC lipids. SDS might influence not only SC barrier function, but also the nucleated layer of epidermis and dermal system associated with inflammation.23 Recently, no correlation was found between the level of epidermal hyperplasia and TEWL increase on the SDS-irritated skin.23 Further work would be needed to determine the effects of surfactants on skin. 

Feingold and his coworkers demonstrated an important role of nuclear hormone receptor on epidermal differentiation and stratum corneum barrier formation. Activation ofPPARa Peroxisome proliferator-activated receptor a by farnesol also stimulated the differentiation of epidermal keratinocytes.42 Cornified envelope formation, involcrin, and transglutaminase protein, and mRNA levels were also increased by the activation of PPARo . Interestingly, the inflammatory response was also inhibited by the treatment.43 They also showed that topical application of PPARo activators accelerated the barrier recovery after tape stripping or acetone treatment and prevented the epidermal hyperplasia induced by repeated barrier disruption.42 Regulation of the nuclear hormone receptor would open a new possibility for improvement of the cutaneous barrier. 

Histamine receptors are related to skin barrier function.44 Three different types of histamine receptors, HI, H2, and H3 have been reported. First, topical application of histamine HI and H2 receptor antagonists accelerated the barrier repair. Histamine itself, H2 receptor agonist, and histamine releaser delayed the barrier repair. Histamine H3 receptor antagonist and agonist did not affect the barrier recovery rate. Topical application of the HI and H2 receptor antagonists prevented the epidermal hyperplasia induced by barrier disruption under low humidity. The mechanism of the relationship between the histamine receptors and the barrier repair process has not been elucidated yet. 

Activation of calcium permeable receptors such as purinergic P2X receptor or NMDA receptor delayed the barrier recovery after barrier disruption and enhanced epidermal hyperplasia induced by barrier disruption.45-47 Topical application of antagonists of these receptors prevented these pathological changes. On the other hand, topical application of agonists of chloride permeable receptors such as GABA(A) receptor or glycine receptor accelerated the barrier repair and prevented the epidermal hyperplasia 46... 

Not only ionotropic receptors but also metabotropic receptors are associated with cutaneous barrier homeostasis. /32-adrenergic receptor antagonist prevented epidermal hyperplasia induced by barrier disruption.48 In the case of metabotropic receptors, the level of intracellular cAMP in the epidermal keratinocytes is associated with cutaneous barrier homeostasis and epidermal hyperplasia.49... 

As described previously, one can induce dry, scaly skin, which shows features very similar to dermatitis such as atopic dermatitis and psoriasis. Use of this experimentally induced dry skin should enable the discovery of a new clinical methodology to cure or care for skin problems. Recently, several excellent in vitro skin models have been reported. Although they are also very useful models for the study of cutaneous metabolism, their function and microstructure are still different from those of intact skin. On the other hand, the mechanisms underlying abnormal desquamation, that is, scaling in the dry skin such as atopic dermatitis, are not completely known. Sato et al. reported55 the inhibition of protease in the SC induced scale without affecting epidermal mitosis. This result seems to be no direct relationship between skin surface appearance and epidermal proliferation. However, decline of SC barrier function induced epidermal hyperplasia, as described earlier.30 The loss of water content from SC also induced epidermal DNA synthesis.30 Further mechanistic studies on each of the dry skin features are required. 

Denda, M., Wood, L.C., Emami, S., Calhoun, C., Brown, B.E., Elias, P.M., and Feingold, K.R. (1996) The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss. Arch. Dermatol. Res. 288 230-238. 

Ashida, Y. and Denda, M. (2001) Histamine HI and H2 receptor antagonists accelerate skin barrier repair and prevent epidermal hyperplasia induced by barrier disruption in a dry environment../. Invest. Dermatol. 116 261-265. 

Denda, M., Kitamura, K., Elias, P.M., and Feingold, K.R. trans-4-(Aminomethyl)cyclohexane carboxlic acid (T-AMCHA), and anti-fibrinolytic agent, accelerates barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans. J. Invest. Dermatol. 109, 84—90 (1997). 

These findings suggest a new pharmacological approach toward altering barrier function or epidermal hyperplasia in healthy and diseased skin with inorganic particles. 

Fuziwara, S., Ogawa, K., Aso, D., Yoshizawa, D., Takata, S. and Denda, M., Barium sulfate with a negative f potential accelerates skin permeable barrier recovery and prevents epidermal hyperplasia indueced by barrier disruption. Br. J. Dermarol. 151 557-564, 2004. 

Abnormalities in lipid lamellar structure or corneodesmolysis are apparent in scaling disorders like X-linked Ichthyosis, atopic dry skin, or in winter xerosis.2,10 Susceptibility to dry skin also shows a tendency to increase with age.3 Exposure to dry environment or extreme shifts in external humidity produces important alterations in underlying skin. Dry environment stimulates epidermal hyperplasia and early markers of inflammation. Shift in external humidity induces a profound defect in... 

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