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Introduction
Michel Simon currently works at the Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), Toulouse University, French National Institut for Health and Medical Research (INSERM), Toulouse, France. Michel does research in Cell Biology and Dermatology. Their most recent publication is 'Prolyl endopeptidase is involved in filaggrinolysis and cornification'.
Current institution
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January 2021 - present
Publications
Publications (210)
Les plasmas froids à pression atmosphérique, des gaz partiellement ionisés, sont utilisés pour diverses applications biomédicales, comme la décontamination des instruments chirurgicaux. Récemment, une méthode dérivée et plus facile à mettre en œuvre a été développée : l’utilisation de milieux activés par plasma froid (PAM). Le traitement des plaies...
Our objectives were to explore epidermal barrier defects in dogs with atopic dermatitis and to determine whether the defects are genetically determined or secondary to skin inflammation. First, the expression of filaggrin, corneodesmosin, and claudin1, analyzed using indirect immunofluorescence in skin biopsies collected from 32 healthy and 32 dogs...
Filaggrin (FLG) is a well-known biomarker of atopic dermatitis and skin dryness. Its full proteolysis (or filaggrinolysis) produces the major constituents of the natural moisturizing factor. Some proteases/peptidases remain to be identified in this multistep process. Mining 16 omics analyses, we identified prolyl endopeptidase (PREP) as a candidate...
Peptidylarginine deiminases (PADs) transform a protein arginine residue into the non-standard amino acid citrulline. This calcium-dependent post-translational modification of proteins is called citrullination or deimination. As described in this special issue, PADs play a role in various physiological processes, and PAD deregulations are involved i...
Deimination is a post-translational modification catalyzed by a family of enzymes named peptidylarginine deiminases (PADs). PADs transform arginine residues of protein substrates into citrulline. Deimination has been associated with numerous physiological and pathological processes. In human skin, three PADs are expressed (PAD1-3). While PAD3 is im...
Absence of a functional proteasome in the suprabasal layers of the epidermis is responsible for keratosis linearis with ichthyosis congenital and sclerosing keratoderma syndrome. Patient epidermis shows hypergranulosis associated with abnormally shaped keratohyalin granules and abnormal distribution of filaggrin in the Stratum granulosum and Stratu...
Epidermal cells integrate multiple signals that activate signaling pathways involved in skin homeostasis. Transforming growth factor β1 (TGF-β1) signaling pathway upregulates miRNA (miR)-21-5p in keratinocytes and is often deregulated in skin diseases. To identify bioactive compounds enable to modulate the TGF-β1/miR-21-5p signaling pathway, we scr...
Atopic dermatitis (AD), the most common inflammatory skin disorder, is a multifactorial disease characterized by a genetic predisposition, epidermal barrier disruption, a strong T helper (Th) type 2 immune reaction to environmental antigens and an altered cutaneous microbiome. Microbial dysbiosis characterized by the prevalence of Staphylococcus au...
Keratoconus (KC) is a multifactorial progressive ectatic disorder characterized by local thinning of the cornea, leading to decreased visual acuity due to irregular astigmatism and opacities. Despite the evolution of advanced imaging methods, the exact etiology of KC remains unknown. Our aim was to investigate the involvement of corneal epithelium...
Cold Atmospheric Plasma (CAP) is an emerging technology with great potential for biomedical applications such as sterilizing equipment and antitumor strategies. CAP has also been shown to improve skin wound healing in vivo, but the biological mechanisms involved are not well known. Our study assessed a possible effect of a direct helium jet CAP tre...
Importance:
Uncombable hair syndrome (UHS) is a rare hair shaft anomaly that manifests during infancy and is characterized by dry, frizzy, and wiry hair that cannot be combed flat. Only about 100 known cases have been reported so far.
Objective:
To elucidate the genetic spectrum of UHS.
Design, setting, and participants:
This cohort study incl...
Among the new biological therapies for atopic diseases, dupilumab is a fully human monoclonal antibody directed against IL-4Rα, the common chain of interleukin-4 and interleukin-13 receptors. Dupilumab showed clinical improvements in patients with atopic dermatitis, asthma, and chronic rhinosinusitis and is currently under development for other ind...
The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filag...
Cold Atmospheric Plasma (CAP) is an emerging physical approach displaying encouraging antitumor and wound healing effects both in vitro and in vivo. In this study, we assessed the potential of direct CAP to remodel skin collagens using an original tissue-engineered human dermal substitute model rich in endogenous extracellular matrix (ECM) covered...
Background
The pathogenesis of human atopic dermatitis (AD) is complex. Like humans, dogs develop spontaneous AD so this species could be a useful model of study. However, AD has been less characterised in dogs than in humans.
Objectives
To compare the epidermis of normal and spontaneously atopic dogs at the functional and structural levels.
Anim...
Résumé
La dermatite atopique (DA), est une dermatose prurigineuse inflammatoire, fréquente et chronique. Elle touche aussi bien les enfants que les adultes. Son étiologie est multifactorielle et implique des interactions complexes entre une prédisposition génétique, une dysrégulation du système immunitaire, une altération de la barrière cutanée et...
Increased presence of interleukin (IL)-22⁺ cells in the skin is a characteristic finding in skin barrier defects, such as atopic dermatitis (AD) and psoriasis. However, mechanistic insights into effects of IL-22 on epidermal functioning is yet to be elucidated. One crucial step during epidermal differentiation is deimination or citrullination. Here...
Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by eczematous and pruritic skin lesions. In recent decades, the prevalence of AD has increased worldwide, most notably in developing countries. The enormous progress in our understanding of the complex composition and functions of the epidermal barrier allows for a deeper...
Deimination (or citrullination) is a post-translational modification catalyzed by a calcium-dependent enzyme family of five peptidylarginine deiminases (PADs). Deimination is involved in physiological processes (cell differentiation, embryogenesis, innate and adaptive immunity, etc.) and in autoimmune diseases (rheumatoid arthritis, multiple sclero...
La désimination, modification post-traductionnelle catalysée par les peptidylarginine désiminases (PADs), favorise la dégradation complète de la filaggrine, essentielle à l’hydratation de la couche cornée et à la barrière épidermique, et contrôle le processus d’autophagie associé à la cornification. Dans l’épiderme humain normal, les PAD1-3 sont ex...
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 numb...
Human filaggrin (FLG) plays a key role in epidermal barrier function, and loss-of-function mutations of its gene are primarily responsible for the development of human atopic dermatitis (AD). FLG expression is also reduced in the epidermis of atopic patients, due to the transcriptional effect of Th2 type cytokines. Canine atopic dermatitis (CAD) is...
Background:
Chronic hand eczema (CHE) is the most common skin disorder affecting the hands. It causes major physical and psychological burden for patients. Classification of CHE remains challenging because of its aetiological and clinical heterogeneity.
Objectives:
Using Latent Class Analysis (LCA) on a large categorical data set, our aim was to...
Background
Chronic hand eczema (CHE) is a major burden for patients. Maintenance treatment involves prevention measures limiting detrimental behaviour and aggravating factors.
Objective
To evaluate the effect of a standardised care program including therapeutic patient education (TPE) on hand care behaviours, clinical severity, quality of life, an...
Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models...
Myosin Vb (Myo5b) is an unconventional myosin involved in the actin-dependent transport and tethering of intracellular organelles. In the epidermis, granular keratinocytes accumulate cytoplasmic lamellar bodies (LBs), secretory vesicles released at the junction with the stratum corneum that participate actively in the maintenance of the epidermal b...
Deimination, a post-translational modification catalyzed by a family of enzymes called peptidylarginine deiminases (PADs), is the conversion of arginine into citrulline residues in a protein. Deimination has been associated with numerous physiological and pathological processes. Our aim was to study its implication in the homeostasis of human epide...
Background
Central centrifugal cicatricial alopecia (CCCA) is the most common form of scarring alopecia among women of African ancestry. The disease is occasionally observed to affect women in families in a manner that suggests an autosomal dominant trait and usually manifests clinically after intense hair grooming. We sought to determine whether t...
Filaggrin (FLG) and corneodesmosin (CDSN) are two key proteins of the human epidermis. FLG loss-of-function mutations are the strongest genetic risk factors for human atopic dermatitis. Studies of the epidermal distribution of canine FLG and CDSN are limited. Our aim was to better characterize the distribution of FLG and CDSN in canine skin. Using...
en Linked Article: Engebretsen et al. Br J Dermatol 2018; 179:679–688.
Deimination or citrullination is a posttranslational modification catalysed by a family of calcium‐dependent enzymes called peptidylarginine deiminases (PADs). It corresponds to the transformation of arginine residues within a peptide sequence into citrulline residues. Deimination induces a decreased net charge of targeted proteins; therefore it al...
Background:
A variety of human skin disorders is characterized by defects in the epidermal barrier, leading to dehydration, itchiness, and rashes. Previously published literature suggests that microtubule stabilization at the cortex of differentiating keratinocytes is necessary for the formation of the epidermal barrier.
Objectives:
We tested wh...
Introduction
L’eczéma chronique des mains (ECM) altère profondément la qualité de vie (QdV) et peut être responsable d’une morbidité importante. Nous avons mené une étude prospective ouverte dans le but d’évaluer l’intérêt d’une prise en charge standardisée avec éducation thérapeutique (ETP) sur la sévérité clinique, la QdV, la productivité au trav...
Introduction
L’eczéma chronique des mains (ECM) est d’origine multifactorielle mettant en jeu prédisposition génétique, facteurs d’irritation, atopie et allergie de contact.
Matériel et méthodes
L’objectif principal de notre étude était de comparer, par une analyse statistique univariée, les caractéristiques moléculaires (expression des gènes de l...
Background:
Deimination (also known as citrullination), the conversion of arginine in a protein to citrulline, is catalyzed by a family of enzymes called peptidylarginine 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 t...
Introduction
La couche cornée forme une barrière vitale protégeant l’organisme contre les agressions extérieures et la déshydratation. Pour être fonctionnelle, elle doit être hydratée quelles que soient les conditions d’humidité atmosphérique grâce, notamment, à un mélange de molécules hygroscopiques appelé facteur naturel d’hydratation (FNH). Le F...
Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and f...
Hornerin (HRNR) shares numerous features with filaggrin, a key contributor to the epidermal barrier functions. The two proteins display a related structural organization, are expressed by the granular keratinocytes as a large precursor processed by proteolysis, and are cross-linked to the cornified cell envelopes. Two main steps in the metabolism o...
Most of the barrier function of the skin is ensured by the outermost layer of the epidermis, the stratum corneum, composed of flattened, anucleated cells called corneocytes, surrounded by a lipid-enriched lamellar matrix. The composition of the stratum corneum is directly dependent on the underlying granular keratinocytes which are the last living...
Hyaluronan (HA) is synthesized by three HA synthases
(HAS1, HAS2, and HAS3) and secreted in the extracellular
matrix. In human skin, large amounts of HA are found in the
dermis. HA is also synthesized by keratinocytes in the epidermis,
although its epidermal functions are not clearly identified
yet. To investigate HA functions, we studied the effec...
Atopic dermatitis (AD) is a multifactorial skin disease with skin barrier damage, progressive sensitization to environmental antigens, and TH2-skewed mediated systemic immune response.1 Synthesis of filaggrin and filaggrin-like stratum corneum proteins is reduced both on lesional and on nonlesional skin of patients with AD irrespective of their FLG...
Background:
Peptidylarginine deiminases (PADs) catalyze deimination (or citrullination), a calcium-dependent post-translational modification involved in several physiological processes and human diseases, such as rheumatoid arthritis and cancer. Deimination of filaggrin (FLG) by PAD1 and PAD3 during the last steps of keratinocyte differentiation i...
La couche cornée assure une fonction de barrière multifonctionnelle vitale pour l’organisme. Les corps lamellaires (CL), structures tubulo-vésiculaires abondantes dans le cytoplasme des kératinocytes granuleux, jouent un rôle majeur dans la formation et le maintien de cette barrière en déversant leur contenu (lipides, lipases, protéases, anti-proté...
The main function of the epidermis is to establish a vital multifunctional barrier between the body and its external environment. A defective epidermal barrier is one of the key features of atopic dermatitis (AD), a chronic and relapsing inflammatory skin disorder that affects up to 20 percent of children and 2-3 percent of adults and often precede...
Atopic dermatitis is a chronic inflammatory skin disease with defects in the epidermal barrier. In a cohort of African-American children, a FLG2 nonsense mutation has been associated with the disease. In the epidermis of European patients, the expression of filaggrin-2, the filaggrin-related protein encoded by FLG2, is decreased. To describe the fu...
We read with great interest the recent article by Tan et al. (1) who looked for the expression of FLG, the gene encoding filaggrin, in the epithelial cells of mucosae of the oral cavity. FLG non-sense mutations are the strongest genetic risk factor for atopic dermatitis (2) and were shown to increase the risk of food sensitization (3). In the epide...
The existence of citrulline in proteins was first described in the skin. In a paper published in Nature in 1958, George Rogers reported citrulline in a protein of hair follicles (Rogers and Simmonds 1958). Twenty-eight years later, Rothnagel and Rogers purified and characterised the corresponding protein and called it trichohyalin (Rothnagel and Ro...
Atopic dermatitis is a chronic inflammatory skin disorder characterized by defects in the epidermal barrier and keratinocyte differentiation. The expression of filaggrin, a protein thought to play a major role in the function of the epidermis, is down-regulated. However, the impact of this deficiency on keratinocytes is not really known. This was i...
La microscopie à force atomique (AFM) est de plus en plus utilisée pour sonder les propriétés mécaniques des cellules. Dans le domaine de la dermatologie, elle n'a été que rarement utilisée pour imager les cornéocytes isolés. De plus, ces cellules ont généralement été caractérisées après avoir été dénaturées. Nous présentons pour la première fois u...
TMEM45A (DERP7, DNAPTP4 or FLJ10134) gene, belonging to the TMEM family encoding predicted transmembrane proteins, is highly expressed in epidermal keratinocytes. To investigate the potential involvement of TMEM45A during the differentiation and keratinization processes, its expression has been characterized in normal human keratinocytes and the pr...
The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative factors for a number of skin diseases, in...
The principal function of the epidermis, the establishment of a multifunctional barrier between the body and its external environment, is mainly provided by the stratum corneum. One of the clinical characteristics of atopic dermatitis is an increase in the permeability of the epidermis. Other alterations of the stratum corneum have been described....
Background:
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disturbed epidermal barrier. In a subset of patients, this is explained by nonsense mutations in the gene encoding filaggrin (FLG).
Objectives:
We sought to evaluate the respective role of FLG mutations and proinflammatory cytokines and to assess the exp...
Reflectance confocal microscopy (RCM) may help to quantify variations of skin pigmentation induced by different stimuli such as UV radiation or therapeutic intervention. The objective of our work was to identify RCM parameters able to quantify in vivo dermis papilla density and epidermis pigmentation potentially applicable in clinical studies. The...
Recent studies have emphasized the importance of heritable and acquired skin barrier abnormalities in common inflammatory diseases such as psoriasis and atopic dermatitis (AD). To date, no comprehensive studies on the effect of experimental barrier disruption on cornified envelope protein expression have been performed.
To analyse the effect of exp...
On human chromosome 1q21, a 2-Mb region called the epidermal differentiation complex comprises many genes encoding structural and regulatory proteins that are of crucial importance for keratinocyte differentiation and stratum corneum properties. Apart from those for involucrin and loricrin, most of the genes are organized in four families: the gene...
Deimination, the conversion of protein-bound arginines into citrullines, is a post-translational modification catalyzed by a peptidylarginine deiminase (Pad). In the epidermis, three Pads are expressed, namely Pad1, 2 and 3, and the major deiminated protein is filaggrin. Deimination of fibrin has been observed in various pathological inflammatory c...
Corneodesmosin (CDSN) was identified 20 years ago by raising monoclonal antibodies against human plantar stratum corneum. The protein is specific to corneodesmosomes, cell-junction structures that, in humans, are found in the epidermis, the hard palate epithelium, and the inner root sheath of the hair follicles. Synthesized by the granular keratino...
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,...
A single-nucleotide polymorphism within the gene encoding hornerin (HRNR) has recently been linked with atopic dermatitis (AD) susceptibility. HRNR shares features with filaggrin, a key protein for keratinocyte differentiation, but conflicting reports have been published concerning its expression in the epidermis, and its role is still unknown. To...
Deimination or citrullination, is a post-translational modification with many facets. It is involved in several basic cellular processes, including gene regulation, embryonic development and terminal differentiation, and also in various pathophysiological mechanisms linked to severe human diseases such as multiple sclerosis and rheumatoid arthritis...
CDSN/CDSN, human corneodesmosin; KLK, kallikrein; SC, stratum corneum
Peptidylarginine deiminases (PADs) catalyze the conversion of protein-bound arginine to citrulline residues. In human epidermis, where filaggrin is the main deiminated protein, three PADs are detected with specific patterns of expression depending on the keratinocyte (KC) differentiation state. Previous characterizations of the PAD-encoding gene pr...
Long-range cis elements are critical regulators of gene transcription, particularly for paralogous genes clustered on a unique chromosomal region. Such are the five PADI genes in 1p35–36 encoding peptidylarginine deiminases. These enzymes catalyze deimination, or citrullination, a calcium-dependent post-translational modification of proteins which...
Corneodesmosin (CDSN) was identified in the early 90 th by raising monoclonal antibodies against human plantar stratum corneum. It is a protein specific to desmosomes that will undergo transformation into corneodesmosomes, i.e. in man, desmosomes of the epidermis, of the three epithelial layers of the inner root sheath of the hair follicles and of...
