A mechanistic target of rapamycin complex 1/2 (mTORC1)/V-Akt murine thymoma viral oncogene homolog 1 (AKT1)/cathepsin H axis controls filaggrin expression and processing in skin, a novel mechanism for skin barrier disruption in patients with atopic dermatitis

• Published in: Journal of allergy and clinical immunology Vol. 139; no. 4; pp. 1228 - 1241
• Main Authors: Naeem, Aishath S., PhD, Tommasi, Cristina, MRes, Cole, Christian, PhD, Brown, Stuart J., PhD, Zhu, Yanan, PhD, Way, Benjamin, MA, BMBCh, MSc, MRCS, Willis Owen, Saffron A.G., DPhil, Moffatt, Miriam, DPhil, Cookson, William O., DPhil, Harper, John I., MBBS, MD, FRCP, FRCPCH, Di, Wei-Li, PhD, Brown, Sara J., MD, FRCPE, Reinheckel, Thomas, PhD, O'Shaughnessy, Ryan F.L., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01.04.2017; Mosby
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Allergy and Immunology; Animals; Arthritis; Atopic Dermatitis and Skin Disease; Blotting, Western; Cathepsin H - deficiency; Cathepsin H - metabolism; Cytokines; Dermatitis; Dermatitis, Atopic - metabolism; Dermatitis, Atopic - pathology; Disruption; Eczema; Filaggrin Proteins; Fluorescent Antibody Technique; Gene expression; Homology; Humans; Immunohistochemistry; Intermediate Filament Proteins - metabolism; Keratinocytes - metabolism; Keratinocytes - pathology; Male; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Mutation; Oligonucleotide Array Sequence Analysis; Oncogenes; Plasmids; Protease; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rapamycin; Rats; Real-Time Polymerase Chain Reaction; Regulatory-Associated Protein of mTOR; Rodents; Signal transduction; Skin - metabolism; Skin - pathology; United Kingdom > UK; FLG; RXRα; mTORC1/2; Mechanistic target of rapamycin complex 1/2; protease; SNP; Atopic dermatitis; shRNA; Filaggrin gene; AKT1; CTSH; filaggrin; Retinoid-X receptor α; WT; skin barrier; AD; Cathepsin H; EM; Electron microscopy; Wild-type; RAPTOR; Glyceraldehyde-3-phosphae dehydrogenase; V-Akt murine thymoma viral oncogene homolog 1; REK; Rat epidermal keratinocyte; Single nucleotide polymorphism; Short hairpin RNA; GAPDH; regulatory associated protein of the MTOR complex 1

Background Filaggrin, which is encoded by the filaggrin gene (FLG) , is an important component of the skin's barrier to the external environment, and genetic defects in FLG strongly associate with atopic dermatitis (AD). However, not all patients with AD have FLG mutations. Objective We hypothe...