Keratinocyte differentiation

In the skin, ENaC is expressed in keratinocytes of the epidermis and in hair follicles. It could play a role in terminal differentiation by modulating keratinocyte calcium signaling. The skin expresses MR, GR, and 11 3HSD2, but the role of aldosterone and glucocorticoids on ENaC activity and keratinocyte differentiation is not yet understood. 

Reiners, J.J. and Rupp, T. (1989). Conversion of xanthine dehydrogenase to xanthine oxidase occurs during keratinocyte differentiation modulation by 12-O-tetradecanoylphorbol-13-acetate. J. Invest. Dermatol. 93, 132—135. 

Vitamin D analogues (calcipotriol, calcitriol, and tacalcitol) are also frequently selected as initial pharmacotherapy in the management of mild to moderate psoriasis.2 These inhibit keratinocyte differentiation and proliferation and maybe antiinflammatory.2 Unlike corticosteroids, tachyphylaxis does not occur with prolonged use. Clearance of lesions should occur after 4 to 6 weeks of treatment.2 Lack of response by 8 weeks... 

Vitamin D and its analogs inhibit keratinocyte differentiation and proliferation and have antiinflammatory effects by reducing IL-8, IL-2, and other cytokines. Use of vitamin D itself is limited by its propensity to cause hypercalcemia. 

As mentioned above, a subgroup of patients with atopic dermatitis has a filaggrin loss-of-function mutation Recently, it was shown that filaggrin expression is reduced in atopic dermatitis even in the absence of any mutation [29]. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression and neutralization of IL-4 and IL-13 improves skin barrier integrity [30]. This indicates that Th-2 lymphocytes directly contribute to the skin barrier defect in atopic dermatitis. 

Yokota, K., and Sawamura, D., 2006, Hailey-Hailey disease with affective disorder Report of a case with novel ATP2CI gene mutation. J. Dermatol. Sci. 43, 150-151 Yoshida, M., Yamasaki, K., Daiho, T., Iizuka, H., and Suzuki, H., 2006, ATP2C1 is specifically localized in the basal layer of normal epidermis and its depletion triggers keratinocyte differentiation. J. Dermatol. Sci. 43, 21-33... 

The stratum corneum consists of denucleated corneocytes filled with cross-linked proteins, while the intercellular space is occupied by lipids synthesized prior to and during cornification [24], Formation of this barrier relies on the cornification of epidermal keratinocytes, which undergo growth arrest, terminal differentiation, and an epidermal-specific cell death, referred to as planned cell death [25], Abnormalities in any of these programmed events may lead to epidermal disorders such as psoriasis, atopic dermatitis, and cancer. Flowever, biological events that enable basal cells (stem cells) to proliferate, differentiate, and commit planned cell death are still poorly understood [10]. The keratinocyte differentiation process can be stimulated by prodifferentiation agents such as extracellular calcium and 1,25-dihydroxy cholecalciferol (referred to as vitamin D3 hereafter) [23], Aberrant or absent differentiation can be found in other skin disorders such as atopic keratosis, seborrheic keratosis, and rosacea. 

Bikle, D.D. et al. Calcium- and vitamin D-regulated keratinocyte differentiation. Mol Cell Endocrinol. Ill, 161, 2001. 

Eckhart, L. et al. Caspase-14 Analysis of gene structure and mRNA expression during keratinocyte differentiation. Biochem Biophys Res Commun. 277, 655, 2000. 

Bikle, D.D., Ratnam, A., Mauro, T.M., Harris, J., and Pillai, S., Changes in calcium responsiveness and handling during keratinocyte differentiation, J. Clin. Invest. 97, 1085-1093,1996. 

Guerrin, M., Simon, M., Montezin, M., Haftek, M., Vincent, C., and Serre, G., Expression cloning of human comeodesmosin proves its identity with the product of the S gene and allows improved characterization of its processing during keratinocyte differentiation,. /. Biol. Chem., 273, 22640, 1998. 

Mehul, B. et al. Carbohydrate expression and modification during keratinocyte differentiation in normal human and reconstructed epidermis, Exp. Dermatol., 12, 53, 2003. 

Won Lim, S. etal. The effect of ursolic and oleanolic acid on permeability barrier function and epidermal keratinocyte differentiation via PPAR alpha. Abstract 83, J. Skin. Barrier. Res., 83,5, 2003. 

Hanley, K. et al. Keratinocyte differentiation is stimulated by activators of the nuclear receptor PPAR alpha, J. Invest. Dermatol., 110, 368, 1998. 

Mao-Qiang, M. etal. Peroxisome proliferator activated receptor gamma activation stimulates keratinocyte differentiation, J. Invest. Dermatol., 123, 305, 2004. 

Jung, E.M., Betancourt-Calle, S., Mann-Blakeney, R. et al. Sustained phospholipase D activation is associated with keratinocyte differentiation. Carcinogenesis 1999 20 569-76. 

Wakita, H., Tokura, Y., Yagi, H., Nishimura, K., Furukawa, F., and Takigawa, M., Keratinocyte differentiation is induced by cell-permeant ceramides and its proliferation is promoted by sphingosine, Arch. Dermatol. Res., 286, 350, 1994. 

Uchida, Y., Hamanaka, S., Matsuda, K., Mimura, K., and Otsuka, F., Effect of a chemically-synthesized acylglucosylceramide, epidermoside, on normal human keratinocyte differentiation, J. Dermatol. Sci.,... 

The epidermis is a stratified, squamous, keratinizing epithelium. The keratinocytes comprise the major cellular component (>90%) and are responsible for the evolution of barrier function. The epidermis per se can be divided into five distinct strata which correspond to the consecutive steps of keratinocyte differentiation. The ultimate result of this differentiation process is formation of the functional barrier layer, the stratum corneum (-0.01 mm). 

Bollinger Bollag W and Bollag RJ (2001) 1,25-Dihydroxyvitamin D(3), phospholipase D and protein kinase C in keratinocyte differentiation. Molecular and Cellular Endocrinology 177, 173-82. 

About 25 different human genes encode the keratins of skin and other soft tissues. Others specify the keratins of hair and nails.Both of these hard tissues as well as claws, hoofs, beaks, horns, scales, quills, and feathers are largely keratin. However, there are additional constituents. During the final stages of keratinocyte differentiation a 15-nm-thick crosslinked sheath of protein, the cornified cell envelope (CE), forms beneath the plasma membrane. Crosslinkages between keratin and other proteins are formed by the action of transglutaminases. " ... 

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