Lowering relative humidity level increases epidermal protein deimination and drives human filaggrin breakdown
| Autor: | Emeline Lhuillier, Hidenari Takahara, Paul R. Thompson, Guy Serre, Valérie Pendaries, Michel Simon, Marie-Claire Méchin, Laura Cau |
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| Přispěvatelé: | CARBILLET, Véronique, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Ibaraki University |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Keratinocytes MESH: Hydrogen-Ion Concentration Hydrolases Climate MESH: Protein-Arginine Deiminases MESH: Skin / metabolism Filaggrin Proteins MESH: Citrulline / chemistry Biochemistry chemistry.chemical_compound MESH: Cross-Linking Reagents / chemistry Intermediate Filament Proteins MESH: Dermatitis Atopic / metabolism [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Citrulline Protein deiminase skin and connective tissue diseases Skin MESH: Middle Aged MESH: Keratinocytes / metabolism medicine.diagnostic_test integumentary system Citrullination Cell Differentiation Hydrogen-Ion Concentration Middle Aged MESH: Keratins / metabolism MESH: Climate Cell biology medicine.anatomical_structure Cross-Linking Reagents MESH: Hydrolases / metabolism [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Microscopy Electron Transmission Keratins Female MESH: Arginine / chemistry Filaggrin Adult MESH: Cell Differentiation Proteolysis Dermatology MESH: Keratinocytes / cytology Arginine Article Dermatitis Atopic 03 medical and health sciences Microscopy Electron Transmission MESH: Humidity Stratum corneum medicine Humans Molecular Biology MESH: Fluorescent Dyes / chemistry Fluorescent Dyes Atopic dermatitis Transepidermal water loss Transglutaminases MESH: Humans Epidermis (botany) Humidity MESH: Adult MESH: Epidermis / metabolism Urocanic acid 030104 developmental biology chemistry Protein-Arginine Deiminases Posttranslational modification Epidermis MESH: Female MESH: Intermediate Filament Proteins / chemistry MESH: Transglutaminases / metabolism |
| Zdroj: | Journal of Dermatological Science Journal of Dermatological Science, 2017, 86 (2), pp.106-113. ⟨10.1016/j.jdermsci.2017.02.280⟩ Journal of Dermatological Science, Elsevier, 2017, 86 (2), pp.106-113. ⟨10.1016/j.jdermsci.2017.02.280⟩ |
| ISSN: | 0923-1811 |
| DOI: | 10.1016/j.jdermsci.2017.02.280⟩ |
| Popis: | International audience; 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 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. |
| Databáze: | OpenAIRE |
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