Defects of corneocyte structural proteins and epidermal barrier in atopic dermatitis

Lamer, Marina Le; Pellerin, Laurence; Reynier, M.O.; Cau, Laura; Pendaries, Valérie; Leprince, Corinne; Méchin, Marie-Claire; Serre, Guy; Paul, C.; Simon, Michel

doi:10.1515/hsz-2015-0141

Cited by 25 publications

(32 citation statements)

References 32 publications

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“…The data also pointed out the deimination of other proteins that were not previously shown to be deiminated, including the keratinocyte proline-rich protein (Table 1). Besides their role as cornified envelope components, filaggrin and filaggrin-2 are two key proteins for the epidermal barrier function, and deimination is a major step in their similar complex metabolism [34,[37][38][39]. Indeed, filaggrin and filaggrin-2 are two basic proteins that interact with and promote the aggregation of keratin intermediate filaments leading to the formation of the intracellular corneocyte matrix.…”

Section: Pads and Deiminated Proteins In The Epidermismentioning

confidence: 99%

Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases

Méchin

Takahara

Simon

2020

IJMS

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Deimination, also known as citrullination, corresponds to the conversion of the amino acid arginine, within a peptide sequence, into the non-standard amino acid citrulline. This post-translational modification is catalyzed by a family of calcium-dependent enzymes called peptidylarginine deiminases (PADs). Deimination is implicated in a growing number of physiological processes (innate and adaptive immunity, gene regulation, embryonic development, etc.) and concerns several human diseases (rheumatoid arthritis, neurodegenerative diseases, female infertility, cancer, etc.). Here, we update the involvement of PADs in both the homeostasis of skin and skin diseases. We particularly focus on keratinocyte differentiation and the epidermal barrier function, and on hair follicles. Indeed, alteration of PAD activity in the hair shaft is responsible for two hair disorders, the uncombable hair syndrome and a particular form of inflammatory scarring alopecia, mainly affecting women of African ancestry.

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Section: Pads and Deiminated Proteins In The Epidermismentioning

confidence: 99%

Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases

Méchin

Takahara

Simon

2020

IJMS

Self Cite

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“…), epidermal proteases, and protease inhibitors, (2) alteration in SC pH, and (3) decrease in skin ceramides, which supports lipid barrier and water retention [99,100]. So far, loss of function mutation in the filaggrin gene represents the most significant genetic factor in the predisposition to AD, although only a fraction of patients (between a few and 50% depending on the populations studied) carry filaggrin mutations [101,102]. …”

Section: Role Of Vitamin D In Certain Inflammatory Skin Diseasesmentioning

confidence: 99%

Vitamin D and the Pathophysiology of Inflammatory Skin Diseases

Umar

Sastry

Ali

et al. 2018

Skin Pharmacol Physiol

142

135

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Background: Vitamin D is a secosteroid, which was initially known for its skeletal role; however, in recent years, its functions in different organs have been increasingly recognized. In this review, we will provide an overview of vitamin D functions in the skin physiology with specific focus on its role in certain inflammatory skin conditions such as psoriasis and atopic dermatitis. Methods: A comprehensive literature search was carried out in PubMed and Google Scholar databases using keywords like “vitamin D,” “skin,” “atopic dermatitis,” and “psoriasis.” Only articles published in English and related to the study topic were included in this review. Results: Vitamin D is integrally connected to the skin for its synthesis, metabolism, and activity. It regulates many physiological processes in the skin ranging from cellular proliferation, differentiation, and apoptosis to barrier maintenance and immune functions. Vitamin D deficiency is associated with the risk of psoriasis and atopic dermatitis, and several clinical/observational studies have suggested the beneficial effect of vitamin D in the therapy of these 2 inflammatory skin disorders. Conclusions: Vitamin D exerts a pleiotropic effect in the skin and could be an important therapeutic option for psoriasis and atopic dermatitis.

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“…In particular, glutamine spontaneously transforms into pyrrolidone-5-carboxylic acid (PCA), a highly hygroscopic molecule, and histidine is modified by histidase to form trans-urocanic acid (UCA), a major UVB-absorbing chromophore [23–25]. The amino acids and their derivatives produced from filaggrin degradation participate in the formation of the NMF, and contribute to skin photoprotection and to stratum corneum hydration and acidification (reviewed in [26]). The low pH of the stratum corneum in turn prevents skin colonization by pathogenic microorganisms, is important for the activity of enzymes involved in lipid synthesis and controls desquamation [27, 28].…”

Section: Introductionmentioning

confidence: 99%

Lowering relative humidity level increases epidermal protein deimination and drives human filaggrin breakdown

Cau

Pendaries

Lhuillier

et al. 2017

Journal of Dermatological Science

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Background Deimination (also known as citrullination), the conversion of arginine in a protein to citrulline, is catalyzed by a family of enzymes called peptidyl-arginine deiminases (PADs). Three PADs are expressed in the epidermis, one of their targets being filaggrin. Filaggrin plays a central role in atopic dermatitis and is a key protein for the epidermal barrier. It aggregates keratins and is cross-linked to cornified envelopes. Following its deimination, it is totally degraded to release free amino acids, contributing to the natural moisturizing factor (NMF). The mechanisms controlling this multistep catabolism in human are unknown. Objective To test whether external humidity plays a role, and investigate the molecular mechanisms involved. Methods Specimens of reconstructed human epidermis (RHEs) produced in humid or dry conditions (>95% or 30–50% relative humidity) were compared. Results RHEs produced in the dry condition presented structural changes, including a thicker stratum corneum and a larger amount of keratohyalin granules. The transepidermal water loss and the stratum corneum pH were decreased whereas the quantity of NMF was greater. This highly suggested that filaggrin proteolysis was up-regulated. The expression/activity of the proteases involved in filaggrin breakdown did not increase while PAD1 expression and the deimination rate of proteins, including filaggrin, were drastically enhanced. Partial inhibition of PADs with Cl-amidine reversed the effect of dryness on filaggrin breakdown. Conclusion These results demonstrate the importance of external humidity in the control of human filaggrin metabolism, and suggest that deimination plays a major role in this regulation.

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Defects of corneocyte structural proteins and epidermal barrier in atopic dermatitis

Cited by 25 publications

References 32 publications

Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases

Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases

Vitamin D and the Pathophysiology of Inflammatory Skin Diseases

Lowering relative humidity level increases epidermal protein deimination and drives human filaggrin breakdown

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