Stratum Corneum Moisturization at the Molecular Level: An Update in Relation to the Dry Skin Cycle

Rawlings, A. V.; Matts, Paul J.

doi:10.1111/j.1523-1747.2005.23726.x

Cited by 302 publications

(289 citation statements)

References 75 publications

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“…Numerous proteases, including calpain 1 (22), furin (36), profilaggrin endoproteinase 1 (37), matriptase (38), channel-activating serine protease 1 (39), and elastase-2 (40), have been identified as being involved either directly or indirectly in the profilaggrin processing to FLG monomers, whereas calpain 1, caspase-14, and bleomycin hydrolase (23) are required for further proteol- ysis of FLG monomers into smaller peptides and free amino acids. The latter are the major components of the so-called natural moisturizing factor (NMF), the main function of which is to contribute to water retention, flexibility of the stratum corneum, and UV protection (21,41,42). We speculated that the same enzymes could be involved in the processing of FLG2.…”

Section: Discussionmentioning

confidence: 99%

Deimination of Human Filaggrin-2 Promotes Its Proteolysis by Calpain 1

Hsu

Henry

Raymond

et al. 2011

Journal of Biological Chemistry

113

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Filaggrin-2 (FLG2), a member of the S100-fused type protein family, shares numerous features with filaggrin (FLG), a key protein implicated in the epidermal barrier functions. Both display a related structural organization, an identical pattern of expression and localization in human epidermis, and proteolytic processing of a large precursor. Here, we tested whether FLG2 was a substrate of calpain 1, a calcium-dependent protease directly involved in FLG catabolism. In addition, deimination being critical for FLG degradation, we analyzed whether FLG2 deimination interfered with its proteolytic processing. With this aim, we first produced a recombinant form of FLG2 corresponding to subunits B7 to B10 fused to a COOH-terminal His tag. Incubation with calpain 1 in the presence of calcium induced a rapid degradation of the recombinant protein and the production of several peptides, as shown by Coomassie Blue-stained gels and Western blotting with anti-FLG2 or anti-His antibodies. MALDI-TOF mass spectrometry confirmed this result and further evidenced the production of non-immunoreactive smaller peptides. The degradation was not observed when a calpain 1-specific inhibitor was added. The calpain cleavage sites identified by Edman degradation were regularly present in the B-type repeats of FLG2. Moreover, immunohistochemical analysis of normal human skin revealed colocalization of FLG2 and calpain 1 in the upper epidermis. Finally, the FLG2 deiminated by human peptidylarginine deiminases was shown to be more susceptible to calpain 1 than the unmodified protein. Altogether, these data demonstrate that calpain 1 is essential for the proteolytic processing of FLG2 and that deimination accelerates this process.In the epidermis, the program of keratinocyte terminal differentiation is an oriented process during which cells of the basal layer undergo a series of metabolic and structural changes throughout their migration to the surface of the tissue. The stratum corneum, the outermost layer of the epidermis, is formed by the stacking of so-called corneocytes, the end products of the process. The stratum corneum functions as an effective barrier between the body and its outside environment, limiting skin dehydration and preventing the penetration of outside pathogens, UV radiation, and exogenous chemicals. It also contributes to mechanical protection of the body. So that this function can be achieved, peculiar structures are formed, such as the cornified cell envelope, a resistant and insoluble protein shell that replaces the plasma membrane, and the intracorneocyte fibrous matrix made by the aggregation of keratin intermediate filaments.

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Section: Discussionmentioning

confidence: 99%

Deimination of Human Filaggrin-2 Promotes Its Proteolysis by Calpain 1

Hsu

Henry

Raymond

et al. 2011

Journal of Biological Chemistry

113

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“…2). These precursors, synthesized (or imported) in the keratinocytes (for a review, see [28]), are transported in the trans-Golgi network where they self-assemble into short stacks within ovoid or tubular structures, the lamellar bodies (LB) [61][62][63]. The molecular organization of the precursors in the LB is not well understood.…”

Section: Formation Of the Lipid Lamellaementioning

confidence: 99%

The physical chemistry of the stratum corneum lipids

Boncheva

2014

Intern J of Cosmetic Sci

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SynopsisThe extracellular matrix of stratum corneum (SC) participates actively in the defensive performance of human skin. Understanding its physicochemical properties is essential for understanding the skin homoeostasis, for the development of efficient therapies for skin disorders and diseases and for ensuring the safety of products designed for topical application. This article summarizes the current knowledge of the composition, self-assembly and molecular organization of the SC lipids, reviews the evidence connecting these parameters and the barrier properties of human skin, and outlines the immediate issues in the field of SC lipid research. R ESUM E: La matrice extracellulaire du stratum corneum (SC) participe activement a la performance d efensive de la peau humaine. Comprendre ses propri et es physico-chimiques est essentielle pour comprendre l'hom eostasie de la peau, pour le d eveloppement de th erapies efficaces pour les troubles et les maladies de la peau, et pour assurer la s ecurit e des produits conc ßus pour une application topique. Cet article r esume les connaissances actuelles sur la composition, l'auto-assemblage, et l'organisation mol eculaire des lipides SC, examine les preuves reliant ces param etres et les propri et es de barri ere de la peau humaine, et d ecrit les probl emes imm ediats dans le domaine de la recherche sur les lipides SC. IntroductionThe field of skin research is replete with opportunities for those intent on working on scientifically interesting topics while making a noticeable, positive difference in people's lives [1]. The range of important problems that the field can help solving is broad. It comprises (i) reducing infant mortality, especially in the developing countries where defective skin barrier is the second major cause of preterm mortality [2][3][4][5][6]; (ii) improving the skin health of some 20-30% of the population in the developed countries which suffer from some sort of skin barrier dysfunction [7,8]; (iii) developing efficient strategies for the dermal and transdermal delivery of drugs and vaccines [9]; (iv) increasing the national and personal security by developing methods to retard or prevent the skin penetration of chemical warfare agents, toxic spills and pesticides [10, 11]; (v) enhancing the safety of topical products (e.g. fragrances, cosmetics, cleansing agents, sunscreens and insect repellents) [12]. Thus, the targets in skin research cover the full spectrum from counter-acting leaky skin and preventing its penetration by chemicals to pushing chemicals through it. One common major problem underlies these diverse topics: our insufficient understanding of the factors that determine skin permeability.Understanding the permeability of human skin to a large extent means understanding the extracellular lipid matrix of the stratum corneum (SC), the topmost skin layer which constitutes the main barrier to transdermal fluxes [13][14][15][16][17][18][19]. As the lipid matrix forms an uninterrupted pathway from the skin surface to the viable skin tissu...

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“…Barrier compromised individuals have elevated epidermal serine proteases [58]. Equally, Rawlings and Matts [59] recently reviewed the importance of good barrier function in reducing inflammation and itching.…”

Section: Cutaneous Irritation In Different Racial Groupsmentioning

confidence: 99%

Ethnic skin types: are there differences in skin structure and function?¹

Rawlings¹

2006

Intern J of Cosmetic Sci

317

277

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SynopsisPeople of skin of colour comprise the majority of the world's population and Asian subjects comprise more than half of the total population of the earth. Even so, the literature on the characteristics of the subjects with skin of colour is limited. Several groups over the past decades have attempted to decipher the underlying differences in skin structure and function in different ethnic skin types. However, most of these studies have been of small scale and in some studies interindividual differences in skin quality overwhelm any racial differences. There has been a recent call for more studies to address genetic together with phenotypic differences among different racial groups and in this respect several large-scale studies have been conducted recently. The most obvious ethnic skin difference relates to skin colour which is dominated by the presence of melanin. The photoprotection derived from this polymer influences the rate of the skin aging changes between the different racial groups. However, all racial groups are eventually subjected to the photoaging process. Generally Caucasians have an earlier onset and greater skin wrinkling and sagging signs than other skin types and in general increased pigmentary problems are seen in skin of colour although one large study reported that East Asians living in the U.S.A. had the least pigment spots. Induction of a hyperpigmentary response is thought to be through signaling by the protease-activated receptor-2 which together with its activating protease is increased in the epidermis of subjects with skin of colour. Changes in skin biophysical properties with age demonstrate that the more darkly pigmented subjects retaining younger skin properties compared with the more lightly pigmented groups. However, despite having a more compact stratum corneum (SC) there are conflicting reports on barrier function in these subjects. Nevertheless, upon a chemical or mechanical challenge the SC barrier function is reported to be stronger in subjects with darker skin despite having the reported lowest ceramide levels. One has to remember that barrier function relates to the total architecture of the SC and not just its lipid levels. Asian skin is reported to possess a similar basal transepidermal water loss (TEWL) to Caucasian skin and similar ceramide levels but upon mechanical challenge it has the weakest barrier function. Differences in intercellular cohesion are obviously apparent. In contrast reduced SC natural moisturizing factor levels have been reported compared with Caucasian and African American skin. These differences will contribute to differences in desquamation but few data are available. One recent study has shown reduced epidermal Cathepsin L2 levels in darker skin types which if also occurs in the SC could contribute to the known skin ashing problems these subjects experience. In very general terms as the desquamatory enzymes are extruded with the lamellar granules subjects with lowered SC lipid levels are expected to have lowered desquamatory enzyme levels...

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Stratum Corneum Moisturization at the Molecular Level: An Update in Relation to the Dry Skin Cycle

Cited by 302 publications

References 75 publications

Deimination of Human Filaggrin-2 Promotes Its Proteolysis by Calpain 1

Deimination of Human Filaggrin-2 Promotes Its Proteolysis by Calpain 1

The physical chemistry of the stratum corneum lipids

Ethnic skin types: are there differences in skin structure and function?¹

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Stratum Corneum Moisturization at the Molecular Level: An Update in Relation to the Dry Skin Cycle

Cited by 302 publications

References 75 publications

Deimination of Human Filaggrin-2 Promotes Its Proteolysis by Calpain 1

Deimination of Human Filaggrin-2 Promotes Its Proteolysis by Calpain 1

The physical chemistry of the stratum corneum lipids

Ethnic skin types: are there differences in skin structure and function?1

Contact Info

Product

Resources

About

Ethnic skin types: are there differences in skin structure and function?¹