1. Madison KC: Barrier function of the skin: “la raison d'etre” of the epidermis. J Invest Dermatol 121(2):231, 2003
2. Saint-Leger D et al: SC lipids in skin xerosis. Dermatologica 178(3):151, 1989
3. Schneider MR, Paus R: Sebocytes, multifaceted epithelial cells: Lipid production and holocrine secretion. Int J Biochem Cell Biol 42(2):181-185, 2010
4. Fluhr JW et al: Glycerol regulates SC hydration in sebaceous gland deficient(asebia) mice. J Invest Dermatol 120(5):728, 2003
5. Winsor T, Burch GE: Differential roles of layers of human epigastric skin on diffusion rate of water. Arch Intern Med 74:428, 1944
6. Blank IH: Further observations on factors which influence the water content of the stratum corneum. J Invest Dermatol 45:249, 1953
7. Oren A et al: In human epidermis, beta-defensin 2 is packaged in lamellar bodies. Exp Mol Pathol 74(2):180, 2003
8. Bouwstra JA, Pilgrim K, Ponec M: Structure of the skin barrier. In: Skin Barrier, edited by PM Elias, KR Feingold. New York, Taylor and Francis, 2006, p. 65
9. Gray GM, Yardley HJ: Different populations of pig epidermal cells: Isolation and lipid composition. J Lipid Res 16(6):441, 1975
10. Elias PM: Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 80:44s, 1983
11. Downing DT et al: Skin lipids: An update. J Invest Dermatol 88(3):2s, 1987
12. Wertz PW: Biochemistry of human stratum corneum lipids. In: Skin Barrier, edited by PM Elias, KR Feingold. New York, Taylor and Francis, 2006, p. 33
13. Proksch E, Elias PM, Feingold KR: Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements. J Clin Invest 85(3):874, 1990
14. Mao-Qiang M, Elias PM, Feingold KR: Fatty acids are required for epidermal permeability barrier function. J Clin Invest 92(2):791, 1993
15. Proksch E et al: Barrier function regulates epidermal lipid and DNA synthesis. Br J Dermatol 128(5):473, 1993
16. Proksch, E: Biosynthesis of fatty acids in skin and their role in epidermal barrier function, in Progress in Inflammation Research. In: Fatty Acids and Inflammatory Skin Diseases, edited by JM Schroeder. Basel, Birkhauser Verlag, 1999, p. 1
17. Proksch E, Feingold KR, Elias PM: Epidermal HMG CoA reductase activity in essential fatty acid deficiency: Barrier requirements rather than eicosanoid generation regulate cholesterol synthesis. J Invest Dermatol 99(2):216-220, 1992
18. Uchida Y, Hamanaka S: Stratum cormeum ceramides: Function, origins, and therapeutic implications. In: Skin Barrier, edited by PM Elias, KR Feingold. New York, Taylor and Francis, 2006, p. 43
19. Holleran WM et al: Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function. J Clin Invest 91(4):1656, 1993
20. Jensen JM et al: Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier. J Clin Invest 104(12):1761, 1999
21. Uchida Y et al: Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J Lipid Res 41(12):2071, 2000
22. Man MQ et al: Basis for improved permeability barrier homeostasis induced by PPAR and LXR activators: Liposensors stimulate lipid synthesis, lamellar body secretion, and post-secretory lipid processing. J Invest Dermatol 126(2):386, 2006
23. Schurer NY: Implementation of fatty acid carriers to skin irritation and the epidermal barrier. Contact Dermatitis 47(4):199, 2002
24. Jiang YJ et al: Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor δ in human keratinocytes. J Biol Chem 284(28):18942-18952, 2009
25. Roop D: Defects in the barrier. Science 267:474, 1995
26. Nemes Z, Steinert PM: Bricks and mortar of the epidermal barrier. Exp Mol Med 31(1):5, 1999
27. Webb A, Li A, Kaur P: Location and phenotype of human adult keratinocyte stem cells of the skin. Differentiation 72(8):387, 2004
28. Williams ML: Ichthyosis: Mechanisms of disease. Pediatr Dermatol 9(4):365, 1992
29. Pullmann H, Lennartz KJ, Steigleder GK: Disturbance of DNA-Synthesis in early psoriasis. Arch Dermatol Res 258(2):211, 1977
30. Candi E, Schmidt R, Melino G: The cornified envelope: A model of cell death in the skin. Nat Rev Mol Cell Biol 6(4):328, 2005
31. Marekov LN, Steinert PM: Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope. J Biol Chem 273(28):17763, 1998
32. Swartzendruber DC et al: Evidence that the corneocyte has a chemically bound lipid envelope. J Invest Dermatol 88(6):709, 1987
33. Proksch E et al: Barrier function regulates epidermal DNA synthesis. J Clin Invest 87(5):1668, 1991
34. Grubauer G, Elias PM, Feingold KR: Transepidermal water loss: The signal for recovery of barrier structure and function. J Lipid Res 30(3):323, 1989
35. Ekanayake-Mudiyanselage S et al: Expression of epidermal keratins and the cornified envelope protein involucrin is influenced by permeability barrier disruption. J Invest Dermatol 111(3):517, 1998
36. Porter RM et al: Gene targeting at the mouse cytokeratin 10 locus: Severe skin fragility and changes of cytokeratin expression in the epidermis. J Cell Biol 132(5):925, 1996
37. Jensen JM et al: Impaired cutaneous permeability barrier function, skin hydration, and sphingomyelinase activity in keratin 10 deficient mice. J Invest Dermatol 115(4):708, 2000
38. Reichelt J et al: Normal ultrastructure, but altered stratum corneum lipid and protein composition in a mouse model for epidermolytic hyperkeratosis. J Invest Dermatol 113(3):329, 1999
39. Presland RB et al: Barrier function in transgenic mice overexpressing K16, involucrin, and filaggrin in the suprabasal epidermis. J Invest Dermatol 123(3):603, 2004
40. Djian P, Easley K, Green H: Targeted ablation of the murine involucrin gene. J Cell Biol 151(2):381, 2000
41. Mildner M et al: Knockdown of filaggrin impairs diffusion barrier function and increases UV sensitivity in a human skin model. J Invest Dermatol 2010 May 6. [Epub ahead of print] PubMed PMID: 20445547.
42. Ishida-Yamamoto A, Iizuka H: Structural organization of cornified cell envelopes and alterations in inherited skin disorders. Exp Dermatol 7(1):1, 1998
43. Koch PJ et al: Lessons from loricrin-deficient mice: Compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein. J Cell Biol 151(2):389, 2000
44. Jensen JM, Proksch E, Elias PM: The stratum corneum of the epidermis in atopic dermatitis. In: Skin Barrier, edited by PM Elias, KR Feingold. New York, Taylor and Francis, 2006, p. 569
45. Elias PM, Fritsch P, Epstein EH: Staphylococcal scalded skin syndrome. Clinical features, pathogenesis, and recent microbiological and biochemical developments. Arch Dermatol 113(2):207, 1977
46. Honari S: Topical therapies and antimicrobials in the management of burn wounds. Crit Care Nurs Clin North Am 16(1):1, 2004
47. Furuse M et al: Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice. J Cell Biol 156(6):1099, 2002
48. Turksen K, Troy
TC: Permeability barrier dysfunction in transgenic mice overexpressing claudin 6.
Development 129(7):1775, 2002
49. Brandner JM, Proksch E: Epidermal barrier function: Role of tight junctions. In: Skin Barrier, edited by PM Elias, KR Feingold. New York, Taylor and Francis, 2006, p. 191
50. Trautmann A et al: The differential fate of cadherins during T-cell-induced keratinocyte apoptosis leads to spongiosis in eczematous dermatitis. J Invest Dermatol 117(4):927, 2001
51. Maretzky T et al: ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Proc Natl Acad Sci U S A 102(26):9182, 2005
52. Elias PM et al: Desmoglein isoform distribution affects stratum corneum structure and function. J Cell Biol 153(2):243, 2001
53. Tunggal JA et al: E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J 24(6):1146, 2005
54. Maretzky T et al: ADAM10-mediated E-cadherin release is regulated by proinflammatory cytokines and modulates keratinocyte cohesion in eczematous dermatitis. J Invest Dermatol 128(7):1737-1746, 2008
55. Djalilian AR et al: Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response. J Clin Invest 116(5), 2006
56. Matsuki M et al: Defective stratum corneum and early neonatal death in mice lacking the gene for transglutaminase 1 (keratinocyte transglutaminase). Proc Natl Acad Sci U S A 95(3):1044, 1998
57. Huber M et al: Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 267(5197):525, 1995
58. Egberts F et al: Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation. J Cell Sci 117(11):2295, 2004
59. Zeeuwen PL et al: The cystatin M/E-cathepsin L balance is essential for tissue homeostasis in epidermis, hair follicles, and cornea. FASEB J 2010 May 21. [Epub ahead of print] PubMed PMID: 20495178.
60. Cheng T et al: The cystatin M/E-controlled pathway of skin barrier formation: Expression of its key components in psoriasis and atopic dermatitis. Br J Dermatol 161(2):253-264, 2009
61. Descargues P et al: Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity. Nat Genet 37(1):56, 2005
62. Briot A et al: Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J Exp Med 206(5):1135-1147, 2009
63. Martin P: Wound healing–Aiming for perfect skin regeneration. Science 276(5309):75, 1997
64. Wood LC et al: Barrier disruption stimulates interleukin-1 alpha expression and release from a pre-formed pool in murine epidermis. J Invest Dermatol 106(3):397, 1996
65. Wood LC et al: Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin Invest 90(2):482, 1992
66. Wang XP et al: The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis. J Invest Dermatol 123(1):124, 2004
67. Menon GK, Grayson S, Elias PM: Ionic calcium reservoirs in mammalian epidermis: Ultrastructural localization by ion-capture cytochemistry. J Invest Dermatol 84(6):508, 1985
68. Menon GK, Elias PM: Ultrastructural localization of calcium in psoriatic and normal human epidermis. Arch Dermatol 127(1):57, 1991
69. Lee SH et al: Calcium and potassium are important regulators of barrier homeostasis in murine epidermis. J Clin Invest 89(2):530, 1992
70. Hitomi K: Transglutaminases in skin epidermis. Eur J Dermatol 15(5):313, 2005
71. Lavrijsen AP et al: Barrier function parameters in various keratinization disorders: Transepidermal water loss and vascular response to hexyl nicotinate. Br J Dermatol 129(5):547, 1993
72. Verboomen H et al: Functional difference between SERCA2a and SERCA2b Ca2+ pumps and their modulation by phospholamban. Biochem J 286:591, 1992
73. Foggia L, Hovnanian A: Calcium pump disorders of the skin. Am J Med Genet C Semin Med Genet 131(1):20, 2004
74. Hu Z et al: Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nat Genet 24(1):61, 2000
75. Denda M: New methodology to improve epidermal barrier homeostasis In: Dry Skin and Moisturizers, edited by M Loden, HI Maibach. New York, Taylor and Francis, 2006, p. 155
76. Gunathilake R et al: Epidermal barrier dysfunction in non-atopic HIV: Evidence for an “inside-to-outside” pathogenesis. J Invest Dermatol 130(4):1185-1188, 2010
77. Berger CL, Edelson R: The life cycle of cutaneous T cell lymphoma reveals opportunities for targeted drug therapy. Curr Cancer Drug Targets 4(7):609, 2004
78. Leung DY: New insights into the complex gene-environment interactions evolving into atopic dermatitis. J Allergy Clin Immunol 118(1):37, 2006
79. Elias PM, Feingold KR: Does the tail wag the dog? Role of the barrier in the pathogenesis of inflammatory dermatoses and therapeutic implications. Arch Dermatol 137(8):1079, 2001
80. Proksch E, Jensen JM, Elias PM: Skin lipids and epidermal differentiation in atopic dermatitis. Clin Dermatol 21(2):134, 2003
81. Proksch E, Foelster-Holst R, Jensen JM: Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci 43(3):159-169, 2006
82. Proksch E et al: Role of the epidermal barrier in atopic dermatitis. J Dtsch Dermatol Ges 7(10):899-910, 2009
83. Palmer CN et al: Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38:441, 2006
84. Ruether A et al: Filaggrin loss-of-function variant contributes to atopic dermatitis risk in the population of Northern Germany. Br J Dermatol 155:1093-1094, 2006
85. Weidinger S et al: Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol 118:214, 2006
86. Irvine AD, McLean WH: Breaking the(un)sound barrier: Filaggrin is a major gene for atopic dermatitis. J Invest Dermatol 126:1200, 2006
87. Akiyama M: FLG mutations in ichthyosis vulgaris and atopic eczema: Spectrum of mutations and population genetics. Br J Dermatol 162(3):472-477, 2010
88. Scott IR, Harding CR: Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol 115:84, 1986
89. Wu Z et al: Highly complex peptide aggregates of the S100 fused-type protein hornerin are present in human skin. J Invest Dermatol 129(6):1446-1458, 2009
90. Walley AJ et al: Gene polymorphism in Netherton and common atopic disease. Nat Genet 29:175, 2001
91. Macheleidt O, Kaiser HW, Sandhoff K: Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol 119(1):166, 2002
92. Fartasch M, Bassukas ID, Diepgen TL: Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics. Br J Dermatol. 127(3):221, 1992
93. Grice K, Sattar H, Baker H: The cutaneous barrier to salts and water in psoriasis and in normal skin. Br J Dermatol 88(5):459, 1973
94. Motta S et al: Abnormality of water barrier function in psoriasis. Role of ceramide fractions. Arch Dermatol 130(4):452, 1994
95. Fartasch M: Epidermal barrier in disorders of the skin. Microsc Res Tech 38(4):361, 1997
96. Segre JA: Epidermal barrier formation and recovery in skin disorders. J Clin Invest 116(5):1150, 2006
97. Epstein EH Jr, Leventhal ME: Steroid sulfatase of human leukocytes and epidermis and the diagnosis of recessive X-linked ichthyosis. J Clin Invest 67(5):1257, 1981
98. Bouwstra JA et al: Cholesterol sulfate and calcium affect stratum corneum lipid organization over a wide temperature range. J Lipid Res 40(12):2303, 1999
99. Thauvin-Robinet C et al: Unique survival in chrondrodysplasia-hermaphrodism syndrome. Am J Med Genet A 132(3):335, 2005
100. Smith FJ et al: Loss-of function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 38:337-342, 2006
101. Jensen JM et al: Different effects of
pimecrolimus and
betamethasone on the skin barrier in patients with atopic dermatitis.
J Allergy Clin Immunol 123(5):1124-1133, 2009. Erratum in:
J Allergy Clin Immunol 124(5):1038, 2009
102. Ghadially R, Halkier-Sörensen L, Elias PM: Effects of petrolatum on stratum corneum structure and function. J Am Acad Dermatol 26:387, 1992
103. Loden M, Andersson
AC, Lindberg M: Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm).
Br J Dermatol 140:264, 1999
104. Tabata N et al: Biophysical assessment of persistent effects of moisturizers after their daily applications: Evaluation of corneotherapy. Dermatology 200:308, 2000
105. Chamlin SL et al: Ceramide-dominant, barrier repair lipids improve childhood atopic dermatitis. Arch Dermatol 137:1110, 2001
106. Berardesca E et al: Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: A multicenter study. Contact Dermatitis 45:280, 2001