Corneocytes formation

During the transition of the mature keratinocyte into the corneocyte, profilaggrin that is released from the keratohyalin granules is dephosphorylated and proteolytically processed to filaggrin monomers. Filaggrin is responsible for the formation of extensive disulfide bonds... 

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. 

It is not yet clear whether the calcium gradient leads to the formation of a mature barrier or the barrier caused the gradient. It may even be both, if the regulation uses a feedback mechanism, as the differentiation will eventually form a barrier leading to the accumulation of calcium ions in the upper epidermis. This high level of calcium will, in turn, guarantee the ongoing process of differentiation toward the formation of corneocytes (horny cells in the SC). The mechanism is thus almost completely autonomous, perpetual, and, if it runs smoothly, requires little correction from the body. 

FIGURE 28.5 (a)Control, nontreated site from a 42-year-old male. The outermost (right) layers contain darkly staining globules in an amorphous matrix. Lamellae are present in deeper corneocyte layers, but Landmann units are rare, (b) Treatment with mineral oil results in the formation of large amorphous phases containing some darkly staining material. Bar = 200 nm. 

Behne, M. Uchida, Y. Seki, T. Ortiz de Montellano, P. Elias, P.M. Holleran, W.M. Omega-hydroxyceramides are required for corneocyte lipid envelope (CLE) formation and normal epidermal permeability barrier function. J. Invest. Dermatol. 2000, 114, 185-192. 

Tretinoin (rehn-a, others) is used to reduce the hyperkeratinization that leads to microcomedone formation, the initial lesion in acne. Follicular corneocytes become less cohesive as a result of shedding of desmosomes, decreasing tonofilaments, and increasing keratinocyte autolysis and intracellular deposition of glycogen. 

The stratum corneum is the outer most layer of nonviable epidermis. It has a thickness of about 10 to 12 pm. The stratum corneum consists of 15 to 25 layers of flattened, stacked, hexagonal, and cornified cells known as corneocytes. Each cell is approximately 40 pm in diameter and 0.5 pm in thickness [Bouwstra, 1997]. The thickness of stratum corneum varies with the site of human body. The body extremities such as palms and soles have a thicker stratum corneum [Walters and Roberts, 2002]. The stratum corneum is characterized by an array of keratin-rich corneocytes surrounded by lipid lamella made of cholesterol, free fatty acids, and ceramides [Bouwstra, 1997]. The corneocytes are arranged in brick and mortar structure. Such structural arrangement creates a tortuous intercellular diffusion pathway for water or any other molecules that transverse the stratum corneum. The hydrophobic lipids that surround these diffusion paths or water pores are organized in tight lamellar structure. The summative effects translate to the formation of a tight permeation barrier [Menon, 2002]. 

Figure 12.15 Formation of the lipid barrier of human skin. The top layer of the epidermis called stratum corneum is a hornified and inert barrier. Its primary functions are regulation of the skin s moisture content and protection of the underlying tissues against external influences. Due to its structure it is often compared to a brick wall in which the non-viable keratin-filled corneocytes are embedded like bricks in a matrix of intercellular lipids. Synthesis of the stratum corneum lipids starts in deeper skin layers, where lipids (mainly glucosylceramides and sphingomyelin) are produced and packaged in so-called lamellar bodies . During differentiation and maturation, these lipids are enzymatically converted to ceramides and finally assembled into densely packed lamellar structures surrounding the corneocytes and filling the intercellular spaces of the stratum corneum.

Water in the SC is necessary to maintain its pliability, elasticity, extensibility and resistance to trauma (Rawlings et al. 1994 Cork 1997) and to control the function of several enzymes that control desmo-some degradation and the formation of natural moisturizing factors (NMF) (Rawlings et al. 1994). When water falls below 5-10 mg/ioo mg of the SC dry weight (Schurer et al. 1991 Thune 1996b), the SC loses suppleness and cracks easily (Rudikoff 1998), the process of desquamation is altered and, instead of the usual unicellular and invisible cell detachment, corneocytes are shed in large visible blocks (Spencer 1988 Marks 1997 Rudikoff 1998). 

The permeability skin barrier, a highly specialized structure responsible for retaining skin moisture, is localized mainly at the stratum corneum (Rudikoff 1998) however, its formation begins deeper in the epidermis and its constituents are progressively modified during the process of keratinization until they reach their highest efficiency in the five layers of the stratum compactum (Rawlings et al. 1994). The modified keratinocytes - the corneocytes - and the intercellular complex lipid matrix in which they are embedded form this specialized structure, which Elias compared to a bricks and mortar model, in which the corneocytes are the bricks and the lipid matrix the mortar (Elias 1983). 

Epidermal effects AHAs have a jjrofound effect on keratinization which is chnicaUy detectable by the formatian of a new stratum comeum. It appears that AHAs modulate this formation through diminished cellular cohesion between corneocytes at the lowest levels of the stratum comeum. 

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