The Role of Tight Junctions and Aquaporins in Skin Dryness

  • J. M. Brandner


The maintenance of optimum water content in the skin and especially in the epidermis is provided by many orchestrated mechanisms. Water uptake into the dermis/epidermis, paracellular and transcellular water transport through the epidermis and water retention as well as controlled water loss in the stratum corneum have to be coordinated. Unbalance of these mechanisms results in dry skin. Following its paracellular route, water has to pass tight junctions before it can get into contact with the stratum corneum. For the transcellular route water channels, formed by so-called aquaporins, are of importance. Here, I will summarize our current knowledge of the involvement of aquaporin-formed pores and tight junctions in epidermal water homeostasis – as well as in other functions – and their putative roles in skin dryness.


Atopic Dermatitis Stratum Corneum HaCaT Cell Merkel Cell Carcinoma AQP3 Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Aburada T, Ikarashi N, Kagami M, Ichikawa Y, Sugitani M, Maniwa A, Ueda H, Toda T, Ito K, Ochiai W, Matsushita R, Miyamoto K, Sugiyama K (2011) Byakkokaninjinto prevents body water loss by increasing the expression of kidney aquaporin-2 and skin aquaporin-3 in KKAy mice. Phytother Res 25:897–903PubMedGoogle Scholar
  2. 2.
    Agre P (2006) The aquaporin water channels. Proc Am Thorac Soc 3:5–13PubMedGoogle Scholar
  3. 3.
    Agren J, Zelenin S, Hakansson M, Eklof AC, Aperia A, Nejsum LN, Nielsen S, Sedin G (2003) Transepidermal water loss in developing rats: role of aquaporins in the immature skin. Pediatr Res 53:558–565PubMedGoogle Scholar
  4. 4.
    Aijaz S, Balda MS, Matter K (2006) Tight junctions: molecular architecture and function. Int Rev Cytol 248:261–298PubMedGoogle Scholar
  5. 5.
    Aono S, Hirai Y (2008) Phosphorylation of claudin-4 is required for tight junction formation in a human keratinocyte cell line. Exp Cell Res 314:3326–3339PubMedGoogle Scholar
  6. 6.
    Arabzadeh A, Troy TC, Turksen K (2007) Changes in the distribution pattern of Claudin tight junction proteins during the progression of mouse skin tumorigenesis. BMC Cancer 7:196PubMedGoogle Scholar
  7. 7.
    Balda MS, Matter K (2009) Tight junctions and the regulation of gene expression. Biochim Biophys Acta 1788:761–767PubMedGoogle Scholar
  8. 8.
    Bellemere G, Von Stetten O, Oddos T (2008) Retinoic acid increases aquaporin 3 expression in normal human skin. J Invest Dermatol 128:542–548PubMedGoogle Scholar
  9. 9.
    Benga G (2009) Water channel proteins (later called aquaporins) and relatives: past, present, and future. IUBMB Life 61:112–133PubMedGoogle Scholar
  10. 10.
    Bollag WB, Xie D, Zheng X, Zhong X (2007) A potential role for the phospholipase D2-aquaporin-3 signaling module in early keratinocyte differentiation: production of a phosphatidylglycerol signaling lipid. J Invest Dermatol 127:2823–2831PubMedGoogle Scholar
  11. 11.
    Bourguignon LY, Ramez M, Gilad E, Singleton PA, Man MQ, Crumrine DA, Elias PM, Feingold KR (2006) Hyaluronan-CD44 interaction stimulates keratinocyte differentiation, lamellar body formation/secretion, and permeability barrier homeostasis. J Invest Dermatol 126:1356–1365PubMedGoogle Scholar
  12. 12.
    Boury-Jamot M, Sougrat R, Tailhardat M, Le Varlet B, Bonte F, Dumas M, Verbavatz JM (2006) Expression and function of aquaporins in human skin: Is aquaporin-3 just a glycerol transporter? Biochim Biophys Acta 1758:1034–1043PubMedGoogle Scholar
  13. 13.
    Brandner JM, Kief S, Grund C, Rendl M, Houdek P, Kuhn C, Tschachler E, Franke WW, Moll I (2002) Organization and formation of the tight junction system in human epidermis and cultured keratinocytes. Eur J Cell Biol 81:253–263PubMedGoogle Scholar
  14. 14.
    Brandner JM, McIntyre M, Kief S, Wladykowski E, Moll I (2003) Expression and localization of tight junction-associated proteins in human hair follicles. Arch Dermatol Res 295:211–221PubMedGoogle Scholar
  15. 15.
    Brandner JM (2009) Tight junctions and tight junction proteins in mammalian epidermis. Eur J Pharm Biopharm 72:289–294PubMedGoogle Scholar
  16. 16.
    Cao C, Sun Y, Healey S, Bi Z, Hu G, Wan S, Kouttab N, Chu W, Wan Y (2006) EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. Biochem J 400:225–234PubMedGoogle Scholar
  17. 17.
    Cao C, Wan S, Jiang Q, Amaral A, Lu S, Hu G, Bi Z, Kouttab N, Chu W, Wan Y (2008) All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. J Cell Physiol 215:506–516PubMedGoogle Scholar
  18. 18.
    Cohn ML, Goncharuk VN, Diwan AH, Zhang PS, Shen SS, Prieto VG (2005) Loss of claudin-1 expression in tumor-associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasms. J Cutan Pathol 32:533–536PubMedGoogle Scholar
  19. 19.
    De Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, Berger AE, Zhang K, Vidyasagar S, Yoshida T, Boguniewicz M, Hata T, Schneider LC, Hanifin JM, Gallo RL, Novak N, Weidinger S, Beaty TH, Leung DY, Barnes KC, Beck LA (2011) Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol 127(773–86):e1–e7PubMedGoogle Scholar
  20. 20.
    Denda M, Sato J, Tsuchiya T, Elias PM, Feingold KR (1998) Low humidity stimulates epidermal DNA synthesis and amplifies the hyperproliferative response to barrier disruption: implication for seasonal exacerbations of inflammatory dermatoses. J Invest Dermatol 111:873–878PubMedGoogle Scholar
  21. 21.
    Dumas M, Langle S, Noblesse E, Bonnet-Duquennoy M, Pelle de Queral D, Tadokoro T, Bonte F (2005) Histological variation of Japanese skin with aging. Int J Cosmet Sci 27:47–50Google Scholar
  22. 22.
    Dumas M, Sadick NS, Noblesse E, Juan M, Lachmann-Weber N, Boury-Jamot M, Sougrat R, Verbavatz JM, Schnebert S, Bonte F (2007) Hydrating skin by stimulating biosynthesis of aquaporins. J Drugs Dermatol 6:s20–s24PubMedGoogle Scholar
  23. 23.
    Ebnet K, Suzuki A, Ohno S, Vestweber D (2004) Junctional adhesion molecules (JAMs): more molecules with dual functions? J Cell Sci 117:19–29PubMedGoogle Scholar
  24. 24.
    Feldmeyer L, Huber M, Fellmann F, Beckmann JS, Frenk E, Hohl D (2006) Confirmation of the origin of NISCH syndrome. Hum Mutat 27:408–410PubMedGoogle Scholar
  25. 25.
    Fisher GJ, Voorhees JJ (1998) Molecular mechanisms of photoaging and its prevention by retinoic acid: ultraviolet irradiation induces MAP kinase signal transduction cascades that induce Ap-1-regulated matrix metalloproteinases that degrade human skin in vivo. J Investig Dermatol Symp Proc 3:61–68PubMedGoogle Scholar
  26. 26.
    Fluhr JW, Mao-Qiang M, Brown BE, Wertz PW, Crumrine D, Sundberg JP, Feingold KR, Elias PM (2003) Glycerol regulates stratum corneum hydration in sebaceous gland deficient (asebia) mice. J Invest Dermatol 120:728–737PubMedGoogle Scholar
  27. 27.
    Fluhr JW, Darlenski R, Surber C (2008) Glycerol and the skin: holistic approach to its origin and functions. Br J Dermatol 159:23–34PubMedGoogle Scholar
  28. 28.
    Fujiyoshi Y, Mitsuoka K, de Groot BL, Philippsen A, Grubmuller H, Agre P, Engel A (2002) Structure and function of water channels. Curr Opin Struct Biol 12:509–515PubMedGoogle Scholar
  29. 29.
    Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. Journal of Cell Biology 156:1099–1111PubMedGoogle Scholar
  30. 30.
    Furuse M, Tsukita S (2006) Claudins in occluding junctions of humans and flies. Trends Cell Biol 16:181–188PubMedGoogle Scholar
  31. 31.
    Garcia N, Gondran C, Menon G, Mur L, Oberto G, Guerif Y, Dal Farra C, Domloge N (2011) Impact of AQP3 inducer treatment on cultured human keratinocytes, ex vivo human skin and volunteers. Int J Cosmet Sci 33:432–442PubMedGoogle Scholar
  32. 32.
    Gruber R, Elias PM, Crumrine D, Lin TK, Brandner JM, Hachem JP, Presland RB, Fleckman P, Janecke AR, Sandilands A, McLean WH, Fritsch PO, Mildner M, Tschachler E, Schmuth M (2011) Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function. Am J Pathol 178:2252–63PubMedGoogle Scholar
  33. 33.
    Haass NK, Houdek P, Wladykowski E, Moll I, Brandner JM (2003) Expression patterns of tight junction proteins in Merkel cell carcinoma. In: Baumann KI, Halata Z, Moll I (eds) The Merkel Cell. Springer, Berlin, HeidelbergGoogle Scholar
  34. 34.
    Hadj-Rabia S, Baala L, Vabres P, Hamel-Teillac D, Jacquemin E, Fabre M, Lyonnet S, De Prost Y, Munnich A, Hadchouel M, Smahi A (2004) Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology 127:1386–1390PubMedGoogle Scholar
  35. 35.
    Haftek M (2009) Tight junction-like structures contribute to the lateral contacts between corneocytes and protect corneodesmosomes from premature degradation. J Invest Dermatol 129:S65Google Scholar
  36. 36.
    Haftek M, Callejon S, Sandjeu Y, Padois K, Falson F, Pirot F, Portes P, Demarne F, Jannin V (2011) Compartmentalization of the human stratum corneum by persistent tight junction-like structures. Experimental Dermatology 20:617–621Google Scholar
  37. 37.
    Hara-Chikuma M, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S, Uchida S, Verkman AS (2005) Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem 280:15493–15496PubMedGoogle Scholar
  38. 38.
    Hara-Chikuma M, Verkman AS (2008) Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing. J Mol Med 86:221–231PubMedGoogle Scholar
  39. 39.
    Hara-Chikuma M, Verkman AS (2008) Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol 28:326–332PubMedGoogle Scholar
  40. 40.
    Hara-Chikuma M, Takahashi K, Chikuma S, Verkman AS, Miyachi Y (2009) The expression of differentiation markers in aquaporin-3 deficient epidermis. Arch Dermatol Res 301:245–252PubMedGoogle Scholar
  41. 41.
    Hara M, Ma T, Verkman AS (2002) Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration, ­elasticity, and barrier recovery. J Biol Chem 277:46616–46621PubMedGoogle Scholar
  42. 42.
    Hara M, Verkman AS (2003) Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Proc Natl Acad Sci U S A 100:7360–7365PubMedGoogle Scholar
  43. 43.
    Hashimoto K (1971) Intercellular spaces of the human epidermis as demonstrated with lanthanum. Journal of Investigative Dermatology 57:17–31PubMedGoogle Scholar
  44. 44.
    Hayashi M, Sakai T, Hasegawa Y, Nishikawahara T, Tomioka H, Iida A, Shimizu N, Tomita M, Awazu S (1999) Physiological mechanism for enhancement of paracellular drug transport. J Control Release 62:141–148PubMedGoogle Scholar
  45. 45.
    Helfrich I, Schmitz A, Zigrino P, Michels C, Haase I, le Bivic A, Leitges M, Niessen CM (2007) Role of aPKC isoforms and their binding partners Par3 and Par6 in epidermal barrier formation. J Invest Dermatol 127:782–791PubMedGoogle Scholar
  46. 46.
    Horie I, Maeda M, Yokoyama S, Hisatsune A, Katsuki H, Miyata T, Isohama Y (2009) Tumor necrosis factor-alpha decreases aquaporin-3 expression in DJM-1 keratinocytes. Biochem Biophys Res Commun 387:564–568PubMedGoogle Scholar
  47. 47.
    Igawa S, Kishibe M, Murakami M, Honma M, Takahashi H, Iizuka H, Ishida-Yamamoto A (2011) Tight junctions in the stratum corneum explain spatial differences in corneodesmosome degradation. Exp Dermatol 20:53–57PubMedGoogle Scholar
  48. 48.
    Ishibashi K, Sasaki S, Fushimi K, Uchida S, Kuwahara M, Saito H, Furukawa T, Nakajima K, Yamaguchi Y, Gojobori T et al (1994) Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells. Proc Natl Acad Sci U S A 91:6269–6273PubMedGoogle Scholar
  49. 49.
    Jacobson EL, Kim H, Kim M, Williams JD, Coyle DL, Coyle WR, Grove G, Rizer RL, Stratton MS, Jacobson MK (2007) A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin. Exp Dermatol 16:490–499PubMedGoogle Scholar
  50. 50.
    Ji C, Yang Y, Yang B, Xia J, Sun W, Su Z, Yu L, Shan S, He S, Cheng L, Wan Y, Bi Z (2011) Trans-Zeatin attenuates ultraviolet induced down-regulation of aquaporin-3 in cultured human skin keratinocytes. Int J Mol Med 26:257–263Google Scholar
  51. 51.
    Kim NH, Lee AY (2011) Reduced aquaporin3 expression and survival of keratinocytes in the depigmented epidermis of vitiligo. J Invest Dermatol 130:2231–2239Google Scholar
  52. 52.
    King LS, Choi M, Fernandez PC, Cartron JP, Agre P (2001) Defective urinary-concentrating ability due to a complete deficiency of aquaporin-1. N Engl J Med 345:175–179PubMedGoogle Scholar
  53. 53.
    Kirschner N, Poetzl C, von den Driesch P, Wladykowski E, Moll I, Behne MJ, Brandner JM (2009) Alteration of tight junction proteins is an early event in psoriasis: putative involvement of proinflammatory cytokines. Am J Pathol 175:1095–1106PubMedGoogle Scholar
  54. 54.
    Kirschner N, Houdek P, Fromm M, Moll I, Brandner JM (2010) Tight junctions form a barrier in human epidermis. Eur J Cell Biol 89:839–842PubMedGoogle Scholar
  55. 55.
    Kirschner N, Bohner C, Rachow S, Brandner JM (2010) Tight junctions: is there a role in dermatology? Arch Dermatol Res 302:483–493PubMedGoogle Scholar
  56. 56.
    Kirschner N, Haftek M, Niessen CM, Behne MJ, Furuse M, Moll I, Brandner JM (2011) CD44 regulates tight-junction assembly and barrier function. J Invest Dermatol 131:932–943PubMedGoogle Scholar
  57. 57.
    Kohler K, Zahraoui A (2005) Tight junction: a co-ordinator of cell signalling and membrane trafficking. Biol Cell 97:659–665PubMedGoogle Scholar
  58. 58.
    Kubo A, Nagao K, Yokouchi M, Sasaki H, Amagai M (2009) External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. J Exp Med 206:2937–2946PubMedGoogle Scholar
  59. 59.
    Kurasawa M, Maeda T, Oba A, Yamamoto T, Sasaki H (2011) Tight junction regulates epidermal calcium ion gradient and differentiation. Biochem Biophys Res Commun 406:506–511PubMedGoogle Scholar
  60. 60.
    Kuroda S, Kurasawa M, Mizukoshi K, Maeda T, Yamamoto T, Oba A, Kishibe M, Ishida-Yamamoto A (2010) Perturbation of lamellar granule secretion by sodium caprate implicates epidermal tight junctions in lamellar granule function. J Dermatol Sci 59:107–114PubMedGoogle Scholar
  61. 61.
    Langbein L, Grund C, Kuhn C, Praetzel S, Kartenbeck J, Brandner JM, Moll I, Franke WW (2002) Tight junctions and compositionally related junctional structures in mammalian stratified epithelia and cell cultures derived therefrom. Eur J Cell Biol 81:419–435PubMedGoogle Scholar
  62. 62.
    Langbein L, Pape U-F, Grund C, Kuhn C, Praetzel S, Moll I, Moll R, Franke WW (2003) Tight junction-related structures in the absence of a lumen: Occludin claudins and tight junction plaque proteins in densely packed cell formations of stratified epithelia and squamous cell carcinomas. European Journal of Cell Biology 82:385–400PubMedGoogle Scholar
  63. 63.
    Leotlela PD, Wade MS, Duray PH, Rhode MJ, Brown HF, Rosenthal DT, Dissanayake SK, Earley R, Indig FE, Nickoloff BJ, Taub DD, Kallioniemi OP, Meltzer P, Morin PJ, Weeraratna AT (2007) Claudin-1 overexpression in melanoma is regulated by PKC and contributes to melanoma cell motility. Oncogene 26:3846–3856PubMedGoogle Scholar
  64. 64.
    Leyvraz C, Charles RP, Rubera I, Guitard M, Rotman S, Breiden B, Sandhoff K, Hummler E (2005) The epidermal barrier function is dependent on the serine protease CAP1/Prss8. J Cell Biol 170:487–496PubMedGoogle Scholar
  65. 65.
    Li J, Tang H, Hu X, Chen M, Xie H (2011) Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing. Australas J Dermatol 51:106–112Google Scholar
  66. 66.
    Liu J, Man WY, Lv CZ, Song SP, Shi YJ, Elias PM, Man MQ (2010) Epidermal permeability barrier recovery is delayed in vitiligo-involved sites. Skin Pharmacol Physiol 23:193–200PubMedGoogle Scholar
  67. 67.
    Ludwig RJ, Zollner TM, Santoso S, Hardt K, Gille J, Baatz H, Johann PS, Pfeffer J, Radeke HH, Schon MP, Kaufmann R, Boehncke WH, Podda M (2005) Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation. J Invest Dermatol 125:969–976PubMedGoogle Scholar
  68. 68.
    Ma T, Hara M, Sougrat R, Verbavatz JM, Verkman AS (2002) Impaired stratum corneum hydration in mice lacking epidermal water channel aquaporin-3. J Biol Chem 277:17147–17153PubMedGoogle Scholar
  69. 69.
    Malminen M, Koivukangas V, Peltonen J, Karvonen SL, Oikarinen A, Peltonen S (2003) Immunohistological distribution of the tight junction components ZO-1 and occludin in regenerating human epidermis. Br J Dermatol 149:255–260PubMedGoogle Scholar
  70. 70.
    Marchini G, Stabi B, Kankes K, Lonne-Rahm S, Ostergaard M, Nielsen S (2003) AQP1 and AQP3, psoriasin, and nitric oxide synthases 1–3 are inflammatory mediators in erythema toxicum neonatorum. Pediatr Dermatol 20:377–384PubMedGoogle Scholar
  71. 71.
    Matsuki M, Yamashita F, Ishida-Yamamoto A, Yamada K, Kinoshita C, Fushiki S, Ueda E, Morishima Y, Tabata K, Yasuno H, Hashida M, Iizuka H, Ikawa M, Okabe M, Kondoh G, Kinoshita T, Takeda J, Yamanishi K (1998) Defective stratum corneum and early neonatal death in mice lacking the gene for transglutaminase 1 (keratinocyte transglutaminase). Proc Natl Acad Sci U S A 95:1044–1049PubMedGoogle Scholar
  72. 72.
    Matsuzaki T, Suzuki T, Koyama H, Tanaka S, Takata K (1999) Water channel protein AQP3 is present in epithelia exposed to the environment of possible water loss. J Histochem Cytochem 47:1275–1286PubMedGoogle Scholar
  73. 73.
    Mertens AE, Rygiel TP, Olivo C, van der Kammen R, Collard JG (2005) The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex. J Cell Biol 170:1029–1037PubMedGoogle Scholar
  74. 74.
    Mirza R, Hayasaka S, Takagishi Y, Kambe F, Ohmori S, Maki K, Yamamoto M, Murakami K, Kaji T, Zadworny D, Murata Y, Seo H (2006) DHCR24 gene knockout mice demonstrate lethal dermopathy with differentiation and maturation defects in the epidermis. J Invest Dermatol 126:638–647PubMedGoogle Scholar
  75. 75.
    Mirza R, Hayasaka S, Kambe F, Maki K, Kaji T, Murata Y, Seo H (2008) Increased expression of aquaporin-3 in the epidermis of DHCR24 knockout mice. Br J Dermatol 158:679–684PubMedGoogle Scholar
  76. 76.
    Morita K, Itoh M, Saitou M, Ando-Akatsuka Y, Furuse M, Yoneda K, Imamura S, Fujimoto K, Tsukita S (1998) Subcellular distribution of tight junction-associated proteins (occludin, ZO-1, ZO-2) in rodent skin. Journal of Investigative Dermatology 110:862–866PubMedGoogle Scholar
  77. 77.
    Morita K, Sasaki H, Furuse K, Furuse M, Tsukita S, Miyachi Y (2003) Expression of claudin-5 in dermal vascular endothelia. Exp Dermatol 12:289–295PubMedGoogle Scholar
  78. 78.
    Morita K, Tsukita S, Miyachi Y (2004) Tight junction-associated proteins (occludin, ZO-1, claudin-1, claudin-4) in squamous cell carcinoma and Bowen’s disease. Br J Dermatol 151:328–334PubMedGoogle Scholar
  79. 79.
    Nakahigashi K, Kabashima K, Ikoma A, Verkman AS, Miyachi Y, Hara-Chikuma M (2011) Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia. J Invest Dermatol 131:865–873PubMedGoogle Scholar
  80. 80.
    Nakakoshi M, Morishita Y, Usui K, Ohtsuki M, Ishibashi K (2006) Identification of a keratinocarcinoma cell line expressing AQP3. Biol Cell 98:95–100PubMedGoogle Scholar
  81. 81.
    Nejsum LN, Kwon TH, Jensen UB, Fumagalli O, Frokiaer J, Krane CM, Menon AG, King LS, Agre PC, Nielsen S (2002) Functional requirement of aquaporin-5 in plasma membranes of sweat glands. Proc Natl Acad Sci U S A 99:511–516PubMedGoogle Scholar
  82. 82.
    Niessen CM (2007) Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol 127:2525–2532PubMedGoogle Scholar
  83. 83.
    Ohnemus U, Kohrmeyer K, Houdek P, Rohde H, Wladykowski E, Vidal S, Horstkotte MA, Aepfelbacher M, Kirschner N, Behne MJ, Moll I, Brandner JM (2008). Regulation of epidermal tight-junctions (TJ) during infection with exfoliative toxin-negative Staphylococcus strains. J Invest Dermatol 128:906–16PubMedGoogle Scholar
  84. 84.
    Olsson M, Broberg A, Jernas M, Carlsson L, Rudemo M, Suurkula M, Svensson PA, Benson M (2006) Increased expression of aquaporin 3 in atopic eczema. Allergy 61:1132–1137PubMedGoogle Scholar
  85. 85.
    Peltonen S, Riehokainen J, Pummi K, Peltonen J (2007) Tight junction components occludin, ZO-1, and claudin-1, -4 and −5 in active and healing psoriasis. Br J Dermatol 156:466–472PubMedGoogle Scholar
  86. 86.
    Pereda Mdel C, Dieamant Gde C, Eberlin S, Werka RM, Colombi D, Queiroz ML, Di Stasi LC (2010) Expression of differential genes involved in the maintenance of water balance in human skin by Piptadenia colubrina extract. J Cosmet Dermatol 9:35–43PubMedGoogle Scholar
  87. 87.
    Pummi K, Malminen M, Aho H, Karvonen S-L, Peltonen J, Peltonen S (2001) Epidermal tight junctions: ZO-1 and occludin are expressed in mature, developing, and affected skin and in vitro differentiating keratinocytes. Journal of Investigative Dermatology 117:1050–1058PubMedGoogle Scholar
  88. 88.
    Rasanen K, Vaheri A (2011) TGF-beta1 causes epithelial-mesenchymal transition in HaCaT derivatives, but induces expression of COX-2 and migration only in benign, not in malignant keratinocytes. J Dermatol Sci 58:97–104Google Scholar
  89. 89.
    Rojek AM, Skowronski MT, Fuchtbauer EM, Fuchtbauer AC, Fenton RA, Agre P, Frokiaer J, Nielsen S (2007) Defective glycerol metabolism in aquaporin 9 (AQP9) knockout mice. Proc Natl Acad Sci U S A 104:3609–3614PubMedGoogle Scholar
  90. 90.
    Roudier N, Ripoche P, Gane P, Le Pennec PY, Daniels G, Cartron JP, Bailly P (2002) AQP3 deficiency in humans and the molecular basis of a novel blood group system, GIL. J Biol Chem 277:45854–45859PubMedGoogle Scholar
  91. 91.
    Saitou M, Furuse M, Sasaki H, Schulzke J-D, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11:4131–4142PubMedGoogle Scholar
  92. 92.
    Schlüter H, Wepf R, Moll I, Franke WW (2004) Sealing the live part of the skin: the integrated meshwork of desmosomes, tight junctions and curvilinear ridge structures in the cells of the uppermost granular layer of the human epidermis. Eur J Cell Biol 83:655–665PubMedGoogle Scholar
  93. 93.
    Schneeberger EE, Lynch RD (2004) The tight junction: a multifunctional complex. Am J Physiol Cell Physiol 286:C1213–C1228PubMedGoogle Scholar
  94. 94.
    Smalley KS, Brafford P, Haass NK, Brandner JM, Brown E, Herlyn M (2005) Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion. Am J Pathol 166:1541–1554PubMedGoogle Scholar
  95. 95.
    Sokabe T, Fukumi-Tominaga T, Yonemura S, Mizuno A, Tominaga M (2011) The TRPV4 channel contributes to intercellular junction formation in keratinocytes. J Biol Chem 285:18749–18758Google Scholar
  96. 96.
    Song X, Xu A, Pan W, Wallin B, Kivlin R, Lu S, Cao C, Bi Z, Wan Y (2008) Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes. Int J Mol Med 22:229–236PubMedGoogle Scholar
  97. 97.
    Sougrat R, Morand M, Gondran C, Barre P, Gobin R, Bonte F, Dumas M, Verbavatz JM (2002) Functional expression of AQP3 in human skin epidermis and reconstructed epidermis. J Invest Dermatol 118:678–685PubMedGoogle Scholar
  98. 98.
    Straseski JA, Gibson AL, Thomas-Virnig CL, Allen-Hoffmann BL (2009) Oxygen deprivation inhibits basal keratinocyte proliferation in a model of human skin and induces regio-specific changes in the distribution of epidermal adherens junction proteins, aquaporin-3, and glycogen. Wound Repair Regen 17:606–616PubMedGoogle Scholar
  99. 99.
    Suarez-Farinas M, Fuentes-Duculan J, Lowes MA, Krueger JG (2011) Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol 131:391–400PubMedGoogle Scholar
  100. 100.
    Sugiyama Y, Ota Y, Hara M, Inoue S (2001) Osmotic stress up-regulates aquaporin-3 gene expression in cultured human keratinocytes. Biochim Biophys Acta 1522:82–88PubMedGoogle Scholar
  101. 101.
    Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S (2000) Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier. Br J Dermatol 143:524–531PubMedGoogle Scholar
  102. 102.
    Troy TC, Rahbar R, Arabzadeh A, Cheung RM, Turksen K (2005) Delayed epidermal permeability barrier formation and hair follicle aberrations in ­Inv-Cldn6 mice. Mech Dev 122:805–819PubMedGoogle Scholar
  103. 103.
    Troy TC, Turksen K (2007) The targeted overexpression of a Claudin mutant in the epidermis of transgenic mice elicits striking epidermal and hair follicle abnormalities. Mol Biotechnol 36:166–174PubMedGoogle Scholar
  104. 104.
    Troy TC, Arabzadeh A, Lariviere NM, Enikanolaiye A, Turksen K (2009) Dermatitis and aging-related barrier dysfunction in transgenic mice overexpressing an epidermal-targeted claudin 6 tail deletion mutant. PLoS One 4:e7814PubMedGoogle Scholar
  105. 105.
    Tunggal JA, Helfrich I, Schmitz A, Schwarz H, Gunzel D, Fromm M, Kemler R, Krieg T, Niessen CM (2005) E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. Embo J 24:1146–1156PubMedGoogle Scholar
  106. 106.
    Turksen K, Troy TC (2002) Permeability barrier dysfunction in transgenic mice overexpressing claudin 6. Development 129:1775–1784PubMedGoogle Scholar
  107. 107.
    Van Itallie CM, Anderson JM (2006) Claudins and epithelial paracellular transport. Annu Rev Physiol 68:403–429PubMedGoogle Scholar
  108. 108.
    Velazquez Pereda Mdel C, Dieamant Gde C, Eberlin S, Nogueira C, Colombi D, Di Stasi LC, de Souza Queiroz ML (2009) Effect of green Coffea arabica L. seed oil on extracellular matrix components and water-channel expression in in vitro and ex vivo human skin models. J Cosmet Dermatol 8:56–62PubMedGoogle Scholar
  109. 109.
    Verbavatz JM, Brown D, Sabolic I, Valenti G, Ausiello DA, Van Hoek AN, Ma T, Verkman AS (1993) Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: a freeze-fracture study. J Cell Biol 123:605–618PubMedGoogle Scholar
  110. 110.
    Verdier-Sevrain S, Bonte F (2007) Skin hydration: a review on its molecular mechanisms. J Cosmet Dermatol 6:75–82PubMedGoogle Scholar
  111. 111.
    Verkman AS (2005) More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci 118:3225–3232PubMedGoogle Scholar
  112. 112.
    Verkman AS (2009) Aquaporins: translating bench research to human disease. J Exp Biol 212:1707–1715PubMedGoogle Scholar
  113. 113.
    Vockel M, Breitenbach U, Kreienkamp HJ, Brandner JM (2010) Somatostatin regulates tight junction function and composition in human keratinocytes. Exp Dermatol 19:888–894PubMedGoogle Scholar
  114. 114.
    Voss KE, Bollag RJ, Fussell N, By C, Sheehan DJ, Bollag WB (2011) Abnormal aquaporin-3 protein expression in hyperproliferative skin disorders. Arch Dermatol Res 303:591–600PubMedGoogle Scholar
  115. 115.
    Watson RE, Poddar R, Walker JM, McGuill I, Hoare LM, Griffiths CE, O’Neill CA (2007) Altered claudin expression is a feature of chronic plaque psoriasis. J Pathol 212:450–458PubMedGoogle Scholar
  116. 116.
    Weber C, Fraemohs L, Dejana E (2007) The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 7:467–477PubMedGoogle Scholar
  117. 117.
    Werling AM, Doerflinger Y, Brandner JM, Fuchs F, Becker JC, Schrama D, Kurzen H, Goerdt S, Peitsch WK (2011) Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel cell carcinomas: heterogeneity and indications for cadherin switching. Histopathology 58:286–303PubMedGoogle Scholar
  118. 118.
    Wilke K, Wepf R, Keil FJ, Wittern KP, Wenck H, Biel SS (2006) Are sweat glands an alternate penetration pathway? Understanding the morphological complexity of the axillary sweat gland apparatus. Skin Pharmacol Physiol 19:38–49PubMedGoogle Scholar
  119. 119.
    Yahagi S, Koike M, Okano Y, Masaki H (2011) Lysophospholipids improve skin moisturization by modulating of calcium-dependent cell differentiation pathway. Int J Cosmet Sci 33:251–256PubMedGoogle Scholar
  120. 120.
    Yamamoto T, Saeki Y, Kurasawa M, Kuroda S, Arase S, Sasaki H (2008) Effect of RNA interference of tight junction-related molecules on intercellular barrier function in cultured human keratinocytes. Arch Dermatol Res 300:517–524PubMedGoogle Scholar
  121. 121.
    Yang J, Meyer M, Muller AK, Bohm F, Grose R, Dauwalder T, Verrey F, Kopf M, Partanen J, Bloch W, Ornitz DM, Werner S (2010) Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis. J Cell Biol 188:935–952PubMedGoogle Scholar
  122. 122.
    Yasui M (2004) Molecular mechanisms and drug development in aquaporin water channel diseases: structure and function of aquaporins. J Pharmacol Sci 96:260–263PubMedGoogle Scholar
  123. 123.
    Yoshida Y, Morita K, Mizoguchi A, Ide C, Miyachi Y (2001) Altered expression of occludin and tight junction formation in psoriasis. Archives of Dermatological Research 293:239–244PubMedGoogle Scholar
  124. 124.
    Yuki T, Haratake A, Koishikawa H, Morita K, Miyachi Y, Inoue S (2007) Tight junction proteins in keratinocytes: localization and contribution to barrier function. Exp Dermatol 16:324–330PubMedGoogle Scholar
  125. 125.
    Yuki T, Hachiya A, Kusaka A, Sriwiriyanont P, Visscher MO, Morita K, Muto M, Miyachi Y, Sugiyama Y, Inoue S (2011) Characterization of tight junctions and their disruption by UVB in human epidermis and cultured keratinocytes. J Invest Dermatol 131:744–752PubMedGoogle Scholar
  126. 126.
    Zheng X, Bollinger-Bollag W (2003) Aquaporin 3 colocates with phospholipase d2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation. J Invest Dermatol 121:1487–1495PubMedGoogle Scholar
  127. 127.
    Zimmerli SC, Hauser C (2007) Langerhans cells and lymph node dendritic cells express the tight junction component claudin-1. J Invest Dermatol 127:2381–2390PubMedGoogle Scholar
  128. 128.
    Zimmerli SC, Kerl K, Hadj-Rabia S, Hohl D, Hauser C (2008) Human epidermal Langerhans cells express the tight junction protein claudin-1 and are present in human genetic claudin-1 deficiency (NISCH syndrome). Exp Dermatol 17:20–23PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Dermatology and VenerologyUniversity-Hospital Hamburg-EppendorfHamburgGermany

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