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Impaired Synthesis of Erythropoietin, Glutamine Synthetase and Metallothionein in the Skin of NOD/SCID/γ nullc and Foxn1 nu/nu Mice with Misbalanced Production of MHC Class II Complex

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Abstract

Most skin pathologies are characterized by unbalanced synthesis of major histocompatability complex II (MHC-II) proteins. Healthy skin keratinocytes simultaneously produce large amounts of MHC-II and regeneration-supporting proteins, e.g. erythropoietin (EPO), EPO receptor (EPOR), glutamine synthetase (GS) and metallothionein (MT). To investigate the level of regeneration-supporting proteins in the skin during misbalanced production of MHC-II, skin sections from nonobese diabetic/severe combined immunodeficient (NOD/SCID)/γ nullc and or Foxn1 nu/nu mice which are a priory known to under- and over-express MHC II, respectively, were used. Double immunofluorescence analysis of NOD/SCID/γ nullc skin sections showed striking decrease in expression of MHC-II, EPO, GS and MT. In Foxn1 nu/nu mouse skin, GS was strongly expressed in epidermis and in hair follicles (HF), which lacked EPO. In nude mouse skin EPO and MHC-II were over-expressed in dermal fibroblasts and they were completely absent from cortex, channel, medulla and keratinocytes surrounding the HF, suggest a role for EPO in health and pathology of hair follicle. The level of expression of EPO and GS in both mutant mice was confirmed by results of Western blot analyses. Strong immunoresponsiveness of EPOR in the hair channels of NOD/SCID/γ nullc mouse skin suggests increased requirements of skin cells for EPO and possible benefits of exogenous EPO application during disorders of immune system accompanied by loss MHC-II in skin cells.

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Abbreviations

CNS:

Central nervous system

CLS:

Confocal laser scanning

EPO:

Erythopoietin

EPOR:

Erythopoietin receptor

GFAP:

Glial fibrillary acidic protein

GFAP-PC:

Glial fibrillary acidic protein producing cells

GS:

Glutamine synthetase

mAb:

Monoclonal antibody

MHC II:

Major histocompatibility class II complex

MT:

Metallothionein

NOD/SCID/γ nullc :

Nonobese diabetic/severe combined immunodeficient nude/nude

OSHF:

Outer sheet of hair follicle

pAb:

Polyclonal antibody

PAGE:

Polyacrylamide gel electrophoresis

PBS:

Phosphate-buffered saline

SMAA:

Smooth muscle alpha-actin

References

  1. Danielyan L, Tolstonog G, Traub P et al (2007) Colocalization of glial fibrillary acidic protein, metallothionein, and MHC II in human, rat, NOD/SCID, and nude mouse skin keratinocytes and fibroblasts. J Invest Dermatol 127:555–563

    Article  CAS  PubMed  Google Scholar 

  2. Hoefakker S, Balk HP, Boersma WJ et al (1995) Migration of human antigen-presenting cells in a human skin graft onto nude mice model after contact sensitization. Immunology 86:296–303

    CAS  PubMed  Google Scholar 

  3. Fan L, Busser BW, Lifsted TQ et al (2003) Antigen presentation by keratinocytes directs autoimmune skin disease. Proc Natl Acad Sci USA 100:3386–3391

    Article  CAS  PubMed  Google Scholar 

  4. Christoph T, Müller-Röver S, Audring H et al (2000) The human hair follicle immune system: cellular composition and immune privilege. Br J Dermatol 142:862–883

    Article  CAS  PubMed  Google Scholar 

  5. Galkowska H, Olszewski WL, Wojewodzka U (2005) Expression of natural antimicrobial peptide beta-defensin-2 and Langerhans cell accumulation in epidermis from human non-healing leg ulcers. Folia Histochem Cytobiol 43:133–136

    CAS  PubMed  Google Scholar 

  6. Ansari AA (1993) A possible role of the MHC-associated invariant chain in rheumatoid arthritis. Semin Arthritis Rheum 23:193–197

    Article  CAS  PubMed  Google Scholar 

  7. Wittmann M, Purwar R, Hartmann C et al (2005) Human keratinocytes respond to interleukin-18: implication for the course of chronic inflammatory skin diseases. J Invest Dermatol 124:1225–1233

    Article  CAS  PubMed  Google Scholar 

  8. Wucherpfennig KW, Yu B, Bhol K et al (1995) Structural basis for major histocompatibility complex (MHC)-linked susceptibility to autoimmunity: charged residues of a single MHC binding pocket confer selective presentation of self-peptides in pemphigus vulgaris. Proc Natl Acad Sci USA 92:11935–11939

    Article  CAS  PubMed  Google Scholar 

  9. Geburek F, Ohnesorge B, Deegen E et al (2005) Alterations of epidermal proliferation and cytokeratin expression in skin biopsies from heavy draught horses with chronic pastern dermatitis. Vet Dermatol 16:373–384

    Article  PubMed  Google Scholar 

  10. Smith MD, Roberts-Thomson PJ (1990) Lymphocyte surface marker expression in rheumatic diseases: evidence for prior activation of lymphocytes in vivo. Ann Rheum Dis 49:81–87

    Article  CAS  PubMed  Google Scholar 

  11. Abrams JR, Kelley SL, Hayes E et al (2000) Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J Exp Med 192:681–694

    Article  CAS  PubMed  Google Scholar 

  12. Huisinga M, Failing K, Reinacher M (2007) MHC class II expression by follicular keratinocytes in canine demodicosis-an immunohistochemical study. Vet Immunol Immunopathol 118:210–220

    Article  CAS  PubMed  Google Scholar 

  13. Gilhar A, Kalish RS (2006) Alopecia areata: a tissue specific autoimmune disease of the hair follicle. Autoimmun Rev 5:64–69

    Article  PubMed  Google Scholar 

  14. Barahmani N, de Andrade M, Slusser JP et al (2008) Human leukocyte antigen class II alleles are associated with risk of alopecia areata. J Invest Dermatol 128:240–243

    Article  CAS  PubMed  Google Scholar 

  15. Nakamura M, Jo J, Tabata Y, Ishikawa O (2008) Controlled delivery of T-box21 small interfering RNA ameliorates autoimmune alopecia (Alopecia Areata) in a C3H/HeJ mouse model. Am J Pathol 172:650–658

    Article  CAS  PubMed  Google Scholar 

  16. Shohat M, Mimouni D, Ben-Amitai D, Sredni B, Sredni D, Shohat B, David M (2005) In vitro cytokine profile in childhood alopecia areata and the immunomodulatory effects of AS-101. Clin Exp Dermatol 30:432–434

    Article  CAS  PubMed  Google Scholar 

  17. Schäffer M, Bongartz M, Hoffmann W et al (2007) MHC-class-II-deficiency impairs wound healing. J Surg Res 138:100–105

    Article  PubMed  Google Scholar 

  18. Boutin AT, Weidemann A et al (2008) Epidermal sensing of oxygen is essential for systemic hypoxic response. Cell 133:223–234

    Article  CAS  PubMed  Google Scholar 

  19. Wang B, Amerio P, Sauder DN (1999) Role of cytokines in epidermal Langerhans cell migration. J Leukoc Biol 66:33–39

    CAS  PubMed  Google Scholar 

  20. Semenza GL (2008) O2 sensing: only skin deep? Cell 133:206–208

    Article  CAS  PubMed  Google Scholar 

  21. Danielyan L, Zellmer S, Sickinger S et al (2009) Keratinocytes as depository of ammonium-inducible glutamine synthetase: age- and anatomy-dependent distribution in human and rat skin. PLoS ONE 4:e4416

    Article  PubMed  Google Scholar 

  22. Li W, Maeda Y, Yuan RR et al (2004) Beneficial effect of erythropoietin on experimental allergic encephalomyelitis. Ann Neurol 56:767–777

    Article  CAS  PubMed  Google Scholar 

  23. Soliz J, Joseph V, Soulage C et al (2005) Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies. J Physiol 568:559–571

    Article  CAS  PubMed  Google Scholar 

  24. Knabe W, Siren AL, Ehrenreich H et al (2005) Expression patterns of erythropoietin and its receptor in the developing spinal cord and dorsal root ganglia. Anat Embryol (Berl) 210:209–219

    Article  CAS  Google Scholar 

  25. Nagai A, Nakagawa E, Choi HB et al (2001) Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes, microglia, and oligodendrocytes grown in culture. J Neuropathol Exp Neurol 60:386–392

    CAS  PubMed  Google Scholar 

  26. Grasso G, Sfacteria A, Passalacqua M et al (2005) Erythropoietin and erythropoietin receptor expression after experimental spinal cord injury encourages therapy by exogenous erythropoietin. Neurosurgery 56:821–827

    Article  PubMed  Google Scholar 

  27. Huang Y, Xiao S, Zhang D (1998) Effects of erythropoietin or nitric oxide synthesis inhibitor on hyperdynamic circulatory state in cirrhotic rats. Zhonghua Yi Xue Za Zhi 78:139–142

    CAS  PubMed  Google Scholar 

  28. Srisawat N, Manotham K, Eiam-Ong S et al (2008) Erythropoietin and its non-erythropoietic derivative: do they ameliorate renal tubulointerstitial injury in ureteral obstruction? Int J Urol 15:1011–1017

    CAS  PubMed  Google Scholar 

  29. Fukushima Y, Yanagisawa M, Yasuda T et al (1989) Erythropoietic activity in culture media conditioned by rat mesangial cells. Tohoku J Exp Med 157:153–162

    Article  CAS  PubMed  Google Scholar 

  30. Maxwell PH, Ferguson DJ, Osmond MK et al (1994) Expression of a homologously recombined erythopoietin-SV40 T antigen fusion gene in mouse liver: evidence for erythropoietin production by Ito cells. Blood 84:1823–1830

    CAS  PubMed  Google Scholar 

  31. Bodó E, Kromminga A, Funk W et al (2007) Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin. FASEB J. 21:3346–3354

    Article  PubMed  Google Scholar 

  32. Haroon ZA, Amin K, Jiang X et al (2003) A novel role for erythropoietin during fibrin-induced wound-healing response. Am J Pathol 163:993–1000

    CAS  PubMed  Google Scholar 

  33. Galeano M, Altavilla D, Cucinotta D et al (2004) Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse. Diabetes 53:2509–2517

    Article  CAS  PubMed  Google Scholar 

  34. Galeano M, Altavilla D, Bitto A et al (2006) Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds. Crit Care Med 34:1139–1146

    Article  CAS  PubMed  Google Scholar 

  35. Wang T, Rumbaugh JA, Nath A et al (2006) Viruses and the brain: from inflammation to dementia. Clin Sci (Lond) 110:393–407

    Article  CAS  Google Scholar 

  36. Danielyan L, Mueller L, Proksch B et al (2005) Similar protective effects of BQ-123 and erythropoietin on survival of neural cells and generation of neurons upon hypoxic injury. Eur J Cell Biol 84:907–913

    Article  CAS  PubMed  Google Scholar 

  37. Zandman-Goddard G, Shoenfeld Y (2002) HIV and autoimmunity. Autoimmun Rev 1:329–337

    Article  CAS  PubMed  Google Scholar 

  38. Stingl G, Rappersberger K, Tschachler E et al (1990) Langerhans cells in HIV-1 infection. J Am Acad Dermatol 22:1210–1217

    Article  CAS  PubMed  Google Scholar 

  39. Rico MJ, Kory WP, Gould EW et al (1987) Interface dermatitis in patients with the acquired immunodeficiency syndrome. J Am Acad Dermatol 16:1209–1218

    Article  CAS  PubMed  Google Scholar 

  40. Kim CM, Vogel J, Jay G et al (1992) The HIV tat gene transforms human keratinocytes. Oncogene 7:1525–1529

    CAS  PubMed  Google Scholar 

  41. Memar OM, Arany I, Tyring SK (1995) Skin-associated lymphoid tissue in human immunodeficiency virus-1, human papillomavirus, and herpes simplex virus infections. J Invest Dermatol 105:99S–104S

    Article  CAS  PubMed  Google Scholar 

  42. Takahashi Y, Ogra Y, Suzuki KT (2005) Nuclear trafficking of metallothionein requires oxidation of a cytosolic partner. J Cell Physiol 202:563–569

    Article  CAS  PubMed  Google Scholar 

  43. Russo AF (2008) Anti-metallothionein IgG and levels of metallothionein in autistic families. Swiss Med Wkly 138:70–77

    CAS  PubMed  Google Scholar 

  44. Watabe S, Hasegawa H, Takimoto K et al (1995) Possible function of SP-22, a substrate of mitochondrial ATP-dependent protease, as a radical scavenger. Biochem Biophys Res Commun 213:1010–1016

    Article  CAS  PubMed  Google Scholar 

  45. Aksenov MY, Aksenova MV et al (1997) Oxidative modification of glutamine synthetase by amyloid beta peptide. Free Radic Res 27:267–281

    Article  CAS  PubMed  Google Scholar 

  46. Seth A, Basuroy S, Sheth P et al (2004) L-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer. Am J Physiol Gastrointest Liver Physiol 287:G510–G517

    Article  CAS  PubMed  Google Scholar 

  47. Ito M, Hiramatsu H, Kobayashi K et al (2002) NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100:3175–3182

    Article  CAS  PubMed  Google Scholar 

  48. Mecklenburg L, Nakamura M, Sundberg JP et al (2001) The nude mouse skin phenotype: the role of Foxn1 in hair follicle development and cycling. Exp Mol Pathol 71:171–178

    Article  CAS  PubMed  Google Scholar 

  49. Mecklenburg L, Tychsen B, Paus R (2005) Learning from nudity: lessons from the nude phenotype. Exp Dermatol 14:797–810

    Article  CAS  PubMed  Google Scholar 

  50. Brissette JL, Li J, Kamimura J et al (1996) The product of the mouse nude locus, Whn, regulates the balance between epithelial cell growth and differentiation. Genes Dev 10:2212–2221

    Article  CAS  PubMed  Google Scholar 

  51. Nagel W, Hartmann H-J, Weser U (1990) Monoclonal antibodies to monomeric rat liver metallothionein-I: the immunoreactivity of lysine residues in metallothionein. Immunol Lett 26:291–295

    Article  CAS  PubMed  Google Scholar 

  52. Jaenicke L, Berson W (1977) Glutamine synthetase from pig brain: binding of adenosine thiphosphate. Hoppe-Seyler’s Z Physiol Chem 358:883–889

    CAS  PubMed  Google Scholar 

  53. Buniatian GH, Hartmann H-J, Traub P et al (2001) Acquisition of blood-tissue barrier supporting features by hepatic stellate cells astrocytes of myofibroblastic phenotype. Inverse dynamics of metallothionein and glial fibrillary acidic protein expression. Neurochem Int 38:373–383

    Article  CAS  PubMed  Google Scholar 

  54. Buniatian GH, Hartmann H-J, Traub P et al (2002) Glial fibrillary acidic protein-positive cells of the kidney are capable of raising a protective biochemical barrier similar to astrocytes: expression of metallothionein in podocytes. Anat Rec 267:296–306

    Article  CAS  PubMed  Google Scholar 

  55. Reizis B, Eisenstein M, Bockoba J et al (1997) Molecular characterization of the diabetes-associated mouse MHC class II protein, I-Ag7. Int Immunol 9:43–51

    Article  CAS  PubMed  Google Scholar 

  56. Ueda T, Yoshino H, Kobayashi K et al (2000) Hematopoietic repopulating ability of cord blood CD34(+) cells in NOD/Shi-scid mice. Stem Cells 18:204–213

    Article  CAS  PubMed  Google Scholar 

  57. Bröcker EB, Echternacht-Happle K, Hamm H et al (1987) Abnormal expression of class I and class II major histocompatibility antigens in alopecia areata: modulation by topical immunotherapy. J Invest Dermatol 88:564–568

    Article  PubMed  Google Scholar 

  58. Köpf-Maier P, Mboneko VF, Merker HJ (1990) Nude mice are not hairless. A morphological study. Acta Anat (Basel) 139:178–190

    Article  Google Scholar 

  59. de Preval C, Lisowska-Grospierre B, Loche M et al (1985) A trans-acting class II regulatory gene unlinked to the MHC controls expression of HLA class II genes. Nature (Lond) 318:291–293

    Article  Google Scholar 

  60. Dröge W (2006) Redox regulation in anabolic and catabolic processes. Curr Opin Clin Nutr Metab Care. 9:190–195

    Article  PubMed  Google Scholar 

  61. Stephens LA, Thomas HE, Kay TW (1997) Protection of NIT-1 pancreatic beta-cells from immune attack by inhibition of NF-kappaB. J Autoimmun 10:293–298

    Article  CAS  PubMed  Google Scholar 

  62. Isogai R, Takahashi M, Aisu K et al (2006) The receptor for erythropoietin is present on cutaneous mast cells. Arch Dermatol Res 297:389–394

    Article  CAS  PubMed  Google Scholar 

  63. Lipski S, Grabbe J, Henz BM (1996) Absence of MHC class II antigen on mast cells at sites of inflammation in human skin. Exp Dermatol 5:120–124

    Article  CAS  PubMed  Google Scholar 

  64. Stephens LA, Thomas HE, Kay TW (1997) Protection of NIT-1 pancreatic beta-cells from immune attack by inhibition of NF-kappaB. J Autoimmun 10:293–298

    Article  CAS  PubMed  Google Scholar 

  65. Figueroa YG, Chan AK et al (2002) NF-kappaB plays a key role in hypoxia inducible factor-1-regulated erythropoietin gene expression. Exp Hematol 30:1419–1427

    Article  CAS  PubMed  Google Scholar 

  66. Zhande R, Karsan A (2007) Erythropoietin promotes survival of primary human endothelial cells through PI3 K-dependent, NF-kappaB-independent upregulation of Bcl-xL. Am J Physiol Heart Circ Physiol 292:H2467–H2474

    Article  CAS  PubMed  Google Scholar 

  67. Chen J, Connor KM, Aderman CM et al (2008) Erythropoietin deficiency decreases vascular stability in mice. J Clin Invest 118:526–533

    CAS  PubMed  Google Scholar 

  68. Jelkmann W (2007) Control of erythropoietin gene expression and its use in medicine. Methods Enzymol 435:179–197

    Article  CAS  PubMed  Google Scholar 

  69. Jia HB, Jin Y, Ji Q et al (2009) Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B. Can J Anaesth 56:597–603

    Article  PubMed  Google Scholar 

  70. Erbil Y, Oztezcan S, Giriş M, Barbaros U, Olgaç V, Bilge H, Küçücük H, Toker G (2005) The effect of glutamine on radiation-induced organ damage. Life Sci 78:376–382

    Article  CAS  PubMed  Google Scholar 

  71. Singleton KD, Beckey VE, Wischmeyer PE (2005) Glutamine prevents activation of NF-κB and stress kinase pathways, attenuates inflammatory cytokine release, and prevents acute respiratory distress syndrome (ARDS) following sepsis. Shock 24:583–589

    Article  CAS  PubMed  Google Scholar 

  72. Mita M, Satoh M, Shimada A et al (2008) Metallothionein is a crucial protective factor against Helicobacter pylori-induced gastric erosive lesions in a mouse model. Am J Physiol Gastrointest Liver Physiol 294:G877–G884

    Article  CAS  PubMed  Google Scholar 

  73. Papouli E, Defais M, Larminat F (2002) Overexpression of metallothionein-II sensitizes rodent cells to apoptosis induced by DNA cross-linking agent through inhibition of NF-kappa B activation. J Biol Chem. 277:4764–4769

    Article  CAS  PubMed  Google Scholar 

  74. Mita M, Imura N, Kumazawa Y et al (2002) Suppressed proliferative response of spleen T cells from metallothionein null mice. Microbiol Immunol 46:101–107

    CAS  PubMed  Google Scholar 

  75. Cherian MG, Kang YJ (2006) Metallothionein and liver cell regeneration. Exp Biol Med (Maywood) 231:138–144

    CAS  Google Scholar 

  76. Lansdown AB (2002) Metallothioneins: potential therapeutic aids for wound healing in the skin. Wound Repair Regen 10:130–132

    Article  PubMed  Google Scholar 

  77. Homoncik M, Jilma-Stohlawetz P, Schmid M et al (2004) Erythropoietin increases platelet reactivity and platelet counts in patients with alcoholic liver cirrhosis: a randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther 20:437–443

    Article  CAS  PubMed  Google Scholar 

  78. Sulkowski MS (2003) Anemia in the treatment of hepatitis C virus infection. Clin Infect Dis 37:S315–S322

    Article  PubMed  Google Scholar 

  79. Jiang Y, Kang YJ (2004) Metallothionein gene therapy for chemical-induced liver fibrosis in mice. Mol Ther 10:1130–1139

    Article  CAS  PubMed  Google Scholar 

  80. Savino C, Pedotti R, Baggi F et al (2006) Delayed administration of erythropoietin and its non-erythropoietic derivatives ameliorates chronic murine autoimmune encephalomyelitis. J Neuroimmunol 172:27–37

    Article  CAS  PubMed  Google Scholar 

  81. Penkowa M, Hidalgo J (2000) Metallothionein I + II expression and their role in experimental autoimmune encephalomyelitis. Glia 32:247–263

    Article  CAS  PubMed  Google Scholar 

  82. Abdel-Mageed AB, Zhao F, Rider BJ et al (2003) Erythropoietin-induced metallothionein gene expression: role in proliferation of K562 cells. Exp Biol Med (Maywood) 228:1033–1039

    CAS  Google Scholar 

  83. Wakida K, Shimazawa M, Hozumi I et al (2007) Neuroprotective effect of erythropoietin, and role of metallothionein-1 and -2, in permanent focal cerebral ischemia. Neuroscience 148:105–114

    Article  CAS  PubMed  Google Scholar 

  84. Suárez I, Bodega G, Fernández B (2002) Glutamine synthetase in brain: effect of ammonia. Neurochem Int 41:123–142

    Article  PubMed  Google Scholar 

  85. Yang M, Butler M (2000) Effect of ammonia on the glycosylation of human recombinant erythropoietin in culture. Biotechnol Prog 16:751–759

    Article  CAS  PubMed  Google Scholar 

  86. Yang M, Butler M (2000) Enhanced erythropoietin heterogeneity in a CHO culture is caused by proteolytic degradation and can be eliminated by a high glutamine level. Cytotechnology 34:83–99

    Article  CAS  PubMed  Google Scholar 

  87. Chun YS, Choi E, Kim GT et al (2000) Zinc induces the accumulation of hypoxia-inducible factor (HIF)-1alpha, but inhibits the nuclear translocation of HIF-1beta, causing HIF-1 inactivation. Biochem Biophys Res Commun 268:652–656

    Article  CAS  PubMed  Google Scholar 

  88. Yoshida Y, Higashi T, Nouso K et al (2001) Effects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis. Acta Med Okayama 55:349–355

    CAS  PubMed  Google Scholar 

  89. Iwata M, Takebayashi T, Ohta H et al (1999) Zinc accumulation and metallothionein gene expression in the proliferating epidermis during wound healing in mouse skin. Histochem Cell Biol 112:283–290

    Article  CAS  PubMed  Google Scholar 

  90. Kruczek C, Görg B, Keitel V et al (2009) Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes. Glia 57:79–92

    Article  PubMed  Google Scholar 

  91. Li H, Zhao Y, Guo Y et al (2007) Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen. J Biol Chem 282:5991–6000

    Article  CAS  PubMed  Google Scholar 

  92. Janes SM, Ofstad TA et al (2004) Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt. J Cell Sci 117:4157–4168

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Genrich V. Tolstonog (Department of Tumor Virology, Heinrich-Pette-Institute for Experimental Virology and Immunology, D-20251 Hamburg, Germany) for the help in CSL microscopy of rat skin sections, Dr. Rolf Gebhardt (Institute for Biochemistry, Medical Faculty, University of Leipzig) for provision of mutant mouse skin preparations.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University Hospital of Tuebingen, Otfried-Mueller Str. 45, 72076, Tuebingen, Germany

    L. Danielyan, M. Buadze & C. H. Gleiter

  2. Interfaculty Institute for Biochemistry, University of Tuebingen, Hoppe-Seyler-Str. 4, 72076, Tuebingen, Germany

    S. Verleysdonk

  3. H. Buniatian Institute of Biochemistry, NAS RA, 5/1, P. Sevag St., 375014, Yerevan, Republic of Armenia

    G. H. Buniatian

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  1. L. Danielyan
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  2. S. Verleysdonk
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  3. M. Buadze
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  4. C. H. Gleiter
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  5. G. H. Buniatian
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Correspondence to G. H. Buniatian.

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Special issue article in honor of Professor Armen Galoyan.

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Danielyan, L., Verleysdonk, S., Buadze, M. et al. Impaired Synthesis of Erythropoietin, Glutamine Synthetase and Metallothionein in the Skin of NOD/SCID/γ nullc and Foxn1 nu/nu Mice with Misbalanced Production of MHC Class II Complex. Neurochem Res 35, 899–908 (2010). https://doi.org/10.1007/s11064-009-0074-x

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