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DFG Research Unit FOR 721/2 Molecular Structure and Function of the Tight Junction |
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Project 9 |
Johanna Brandner, Prof. PhD
Dept. of Dermatology and Venerology,
University Hamburg-Eppendorf
Barrier function of tight junctions in keratinocytea, dermal equivalents and skin
The skin is an important barrier of the body that prevents the uncontrolled loss of water and electrolytes as well as the uptake of external substances.
Tight junction (TJ) proteins have been detected in the multilayered epithelium of the epidermis of mice and humans. Studies in mice, which lack distinct TJ proteins in the epidermis, showing a decrease of epidermal barrier function. In cultured human and murine keratinocytes it has been shown that they form functional TJs with normal transepithelial resistance and low permeability for molecular tracers. It is an open so far to what extent these results are applicable to human epidermis or skin. Also unknown is whether TJs exhibit a selective permeability in keratinocytes and in the epidermis and which TJ molecules play an important role.
Therefore, the barrier function of keratinocyte TJs for tracers of different size and charge will be studied. As model systems serve cultured keratinocytes, skin equivalents, and ex vivo specimens of healthy and psoriatic skin. Special emphasis will be placed on the transferability of results from primary keratinocyte cultures on skin equivalents and skin.
Granted by project 9
Dr. Nina Kirschner
Kirschner N*, Rosenthal R* (*shared first authorship), Furuse M, Moll I, Fromm M, Brandner JM (2013) Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes. J. Invest. Dermatol. 133(5): 1161-1169 (IF 6.3) [PubMed] [WebPage] [PDF] [Supplement] For this paper, authors gained the Heinz-Maurer Award for Dermatological Science 2014 (10 T€)
Rachow S*, Zorn-Kruppa M* (*shared first authorship), Ohnemus U, Kirschner N, Vidal-y-Sy S, von den Driesch P, Eberle J, Mildner M, Vettorazzi E, Rosenthal R, Moll I, Brandner JM (2013) Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis. PLoS One 8(2): e55116 (IF 4.1) [PubMed] [WebPage] [PDF] TP9+TP1
Hahne M, Zorn-Kruppa M, Guzman G, Brandner JM, Haltner-Ukomado E, Wätzig H, Reichl S (2012) Prevalidation of a human cornea construct as an alternative to animal corneas for in vitro drug absorption studies. J. Pharm. Sci. (IF 3.0) 101(8): 2976-2888 [PubMed] [WebPage] [PDF] TP9
Kirschner N, Rosenthal R, Günzel D, Moll I, Brandner JM (2012) Tight junctions and differentiation – a chicken or the egg question? Exp. Dermatol. 21(3): 171-175 (IF 4.2) [PubMed] [WebPage] [PDF] TP9+TP1+TP7
Reviews
Kirschner N, Brandner JM (2012) Barriers and more: functions of tight junction proteins in the skin. Ann. N.Y. Acad. Sci. 1257: 158-166 (IF 3.2) [PubMed] [WebPage] [PDF] (Review)
Gruber R, Elias PM, Crumrine D, Lin TK, Brandner JM, Hachem JP, Presland RB, Fleckman P, Janecke AR, Sandilands A, McLean WHI, 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(5): 2252-2263 [PubMed] [WebPage] [PDF]
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(4): 932-943 [PubMed] [WebPage] [PDF] [Supplements]
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(2): 286-303 [PubMed] [WebPage] [PDF]
Kirschner N, Houdek P, Fromm M, Moll I, Brandner JM (2010) Tight junctions form a barrier in human epidermis. Eur. J. Cell Biol. 89(11): 839-842 (IF 3.6) [PubMed] [WebPage] [PDF] TP9+TP1
Vockel M, Breitenbach U, Kreienkamp HJ, Brandner JM (2010) Somatostatin regulates tight junction function and composition in human keratinocytes. Exp. Dermatol. 19(10): 888-894 [PubMed] [WebPage] [PDF]
Reviews
Kirschner N, Brandner JM (2012) Barriers and more: functions of tight junction proteins in the skin. Ann. N.Y. Acad. Sci. 1257: 158-166 (IF 3.2) [PubMed] [WebPage] [PDF] (Review)
Brandner JM*, Haftek M*, Niessen CM* (*shared first authorship) (2010) Adherens junctions, desmosomes and tight junctions in epidermal barrier function. Open Dermatol. J. 4: 14-20 (DOI: 10.2174/1874372201004010014). [Abstract] [PDF] (Review)
Kirschner N, Bohner C, Rachow S, Brandner JM (2010) Tight junctions: is there a role in dermatology? Arch. Dermatol. Res. 302(7): 483-493 [PubMed] [WebPage] [PDF] (Review)
Previous work
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(3): 1095-1106 [PubMed] [WebPage] [PDF]
Eispert AC, Fuchs F, Brandner JM, Houdek P, Wladykowski E, Moll I (2009) Evidence for distinct populations of human Merkel cells. Histochem. Cell. Biol. 132(1): 83-93 [PubMed] [WebPage] [PDF]
Liew CW, Vockel M, Glassmeier G, Brandner JM, Fernandez-Ballester GJ, Schwarz JR, Schulz S, Buck F, Serrano L, Richter D, Kreienkamp HJ (2009) Interaction of the human somatostatin receptor 3 with the multiple PDZ domain protein MUPP1 enables somatostatin to control permeability of epithelial tight junctions. FEBS Lett. 583(1): 49-54 [PubMed] [WebPage]
Brandner JM (2009) Tight junctions and tight junction proteins in mammalian epidermis. Eur. J. Pharm. Biopharm. 72(2): 289-294 [PubMed] [WebPage] [PDF] (Review)
Brandner JM, Zacheja, S, Houdek P, Moll I, Lobmann R (2008) Expression of matrix metalloproteinases, cytokines and connexins in diabetic and non-diabetic human keratinocytes before and after transplantation into an ex-vivo wound healing model. Diabetes Care 31: 114-120.
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 during infection with exfoliative toxin-negative Staphylococcus strains. J. Invest. Dermatol 128: 906-916.
Ohnemus U, Willers C, Bubenheim M, Hostkotte, MA, Houdek P, Fischer F, Schmage, P, Moll I, Brandner JM (2008) An ex-vivo oral mucosa infection model for the evaluation of the topical activity of antifungal agents. Mycoses 51: 21-29.
Proksch E, Brandner JM, Jensen JM (2008). The skin: an indispensable barrier. Exp. Dermatol. 17(12): 1063-1072.
Rickelt S, Franke WW, Doerflinger Y, Goerdt S, Brandner JM, Peitsch WK (2008) Subtypes of melanocytes and melanoma cells distinguished by their intercellular contacts: heterotypic adherens junctions, adhesive associations, and dispersed desmoglein 2 glycoproteins. Cell Tissue Res. 334(3): 401-422.
Neub A, Houdek P, Ohnemus U, Moll I, Brandner JM (2007) Biphasic regulation of AP-1 subunits during human epidermal wound healing. J. Invest. Dermatol. 127: 2453-2462.
Brandner JM, Behne M, Hüsing B, Moll I (2006) Caffeine improves barrier function in male skin. Int. J. Cosmet. Sci. 28: 343-348.
Haass NK, Wladykowski E, Kief S, Moll I, Brandner JM (2006) Differential induction of connexins 26 and 30 in skin tumors and their adjacent epidermis. J. Histochem. Cytochem. 54: 171-182.
Sanchez-Hanke M, Kief S, Leuwer R, Koch U, Moll I, Brandner JM (2005) In vitro iso-lation and cell culture of vestibular inner ear melanocytes. Audiol. Neurootol. 10: 191-200.
Smalley KSM, Brafford P, Haass NK, Brandner JM, Brown E, Herlyn M (2005) Upregulated expression of Zonula Occludens (ZO) protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion. Am. J. Pathol. 166: 1541-1554.
Brandner JM, Houdek P, Hüsing B, Kaiser C, Moll I (2004) Connexins 26, 30 and 43: Differences between spontaneous, chronic and accelerated human wound healing. J. Invest. Dermatol. 122: 1310-1320.
Jonsson M, Bjorntorp-Mark E, Brantsing C, Brandner JM, Lindahl A, Asp J (2004) Hash4, a novel human achaetescute homologue found in fetal skin. Genomics 84: 859-866.
Not peer reviewed
Brandner JM, Poetzl C, Schmage P, Hauswirth U, Moll I (2008) A (leaky?) barrier: Tight junction proteins in skin diseases. Drug Discov. Today: Disease Mechanisms 5(1): e39-e45 (doi:10.1016/j.ddmec.2008.04.007) [WebPage] [PDF]
Brandner JM, Kief S, Wladykowski E, Houdek P, Moll I (2006) Tight Junction proteins in the skin. Skin Pharmacol. Physiol. 19: 71-77.