[en] Background Vascular alterations are significant events in the pathomechanism of psoriasis. A disorder in the mechanisms regulating skin angiogenesis and lymphangiogenesis could participate in the pathogenesis of the disease.
Objectives To quantify differences in the expression of angiogenesis and lymphangiogenesis growth factors, receptors, coreceptors as well as their antagonists in the uninvolved skin of patients with psoriasis compared with the skin of nonpsoriatic volunteers.
Methods Skin biopsies were collected from the involved skin of 13 patients with untreated plaque-type psoriasis, from their nonlesional skin at distance from the lesions and from the skin of 16 healthy volunteers. The mRNA steady-state level of keratins 10, 14 and 16, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), vimentin, collagen I and IV, proliferating cell nuclear antigen, the various splice variants of vascular endothelial growth factor, VEGF-A, VEGF-C and VEGF-D, their receptors VEGFR1, VEGFR2 and VEGFR3, neuropilin (NRP)-1 and its soluble forms, NRP-2, semaphorin 3A and prox-1, was measured by reverse transcription–polymerase chain reaction. Immunohistochemistry was performed for Ki-67, von Willebrand factor and D2-40. Blood and lymphatic vessel density, area and distance from epidermis were estimated by morphological analysis coupled to an original computer-assisted method of quantification.
Results Skin from healthy volunteers and nonlesional skin from patients with psoriasis displayed similar histological, morphometric and proliferative features. However, a significant overexpression of VEGFR3, the VEGF-A isoform VEGF121, soluble 12 NRP-1 and GAPDH was observed in the nonlesional psoriatic skin as compared with that of normal volunteers.
Conclusions These data point to significant differences in the blood and lymphatic vascular transcriptome between the clinically normal-appearing skin of patients with psoriasis and the skin of volunteers without psoriasis.
Henno, Audrey ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Blacher, Silvia ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Lambert, Charles ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Colige, Alain ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Seidel, Laurence ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Nusgens, Betty ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Altered expression of angiogenesis and lymphangiogenesis markers in the uninvolved skin of plaque-type psoriasis
Braverman IM, Yen A. Ultrastructure of the capillary loops in the dermal papillae of psoriasis. J Invest Dermatol 1977 68 : 53 60.
de la Brassinne M, Lachapelle JM. 3H-thymidine labelling of epidermis and dermal infiltrate in psoriatic erythroderma. Acta Derm Venereol (Stockh) 1975 55 : 171 4.
Creamer D, Sullivan D, Bicknell R et al. Angiogenesis and psoriasis. Angiogenesis 2002 5 : 231 6.
Lowe PM, Lee ML, Jackson CJ et al. The endothelium in psoriasis. Br J Dermatol 1995 132 : 497 505.
Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 2007 8 : 464 78.
Detmar M, Brown LF, Claffey KP et al. Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 1994 180 : 1141 6.
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003 9 : 669 76.
Mineur P, Colige A, Deroanne C et al. Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents. J Cell Biol 2007 179 : 1261 73.
Cianfarani F, Zambruno G, Brogelli L et al. Placenta growth factor in diabetic wound healing: altered expression and therapeutic potential. Am J Pathol 2006 169 : 1167 82.
Cao Y, Ji WR, Qi P et al. Placenta growth factor: identification and characterization of a novel isoform generated by RNA alternative splicing. Biochem Biophys Res Commun 1997 235 : 493 8.
Yang W, Ahn H, Hinrichs M et al. Evidence of a novel isoform of placental growth factor (PlGF-4) expressed in human trophoblast and endothelial cells. J Reprod Immunol 2003 60 : 53 60.
Karkkainen M, Haiko P, Sainio K et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 2004 5 : 74 80.
Partanen TA, Arola J, Saaristo A et al. VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissues. FASEB J 2000 14 : 2087 96.
Bhawan J, Bansal C, Whren K et al. K16 expression in uninvolved psoriatic skin: a possible marker of pre-clinical psoriasis. J Cutan Pathol 2004 31 : 471 6.
Lizzul PF, Aphale A, Malaviya R et al. Differential expression of phosphorylated NF-κB/RelA in normal and psoriatic epidermis and downregulation of NF-κB in response to treatment with etanercept. J Invest Dermatol 2005 124 : 1275 83.
Körver JEM, van Duijnhoven MW, Pasch MC et al. Assessment of epidermal subpopulations and proliferation in healthy skin, symptomless and lesional skin of spreading psoriasis. Br J Dermatol 2006 155 : 688 94.
Mordovtsev V, Albanova V. Morphology of skin microvasculature in psoriasis. Am J Dermatopathol 1989 11 : 33 42.
Barton SP, Abdullah MS, Marks R. Quantification of microvascular changes in the skin in patients with psoriasis. Br J Dermatol 1992 126 : 569 74.
De Boer OJ, Wakelkamp IMJ, Pals ST et al. Increased expression of adhesion receptors in both lesional and non-lesional psoriatic skin. Arch Dermatol Res 1994 286 : 304 11.
Tsatsaris V, Goffin F, Munaut C et al. Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab 2003 88 : 5555 63.
Rakic JM, Lambert V, Devy L et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci 2003 44 : 3186 93.
Lambert C, Colige A, Munaut C et al. Distinct pathways in the over-expression of matrix metalloproteinases in human fibroblasts by relaxation of mechanical tension. Matrix Biol 2001 20 : 397 408.
Nusgens BV, Humbert P, Rougier A et al. Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. J Invest Dermatol 2001 116 : 853 9.
Deroanne C, Bonjean K, Servotte S et al. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signalling. Oncogene 2002 21 : 427 36.
Hajitou A, Sounni NE, Devy L et al. Down-regulation of vascular endothelial growth factor by tissue inhibitor of metalloproteinase-2: effect on in vivo mammary tumor growth and angiogenesis. Cancer Res 2001 61 : 3450 7.
Paladini R, Coulombe P. The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 null phenotype by keratin 16. J Cell Biol 1999 146 : 1185 201.
Saharinen P, Tammela T, Karkkainen M et al. Lymphatic vasculature: development, molecular regulation and role in tumor metastasis and inflammation. Trends Immunol 2004 25 : 387 94.
Favier B, Alam A, Barron P et al. Neuropilin-2 interacts with VEGFR2 and VEGFR3 and promotes human endothelial cell survival and migration. Blood 2006 108 : 1243 50.
Hong YK, Shin JW, Detmar M. Development of the lymphatic vascular system: a mystery unravels. Dev Dyn 2004 231 : 462 73.
Karkkainen MJ, Saaristo A, Jussila L et al. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci U S A 2001 98 : 12677 82.
Gagnon ML, Bielenberg D, Gechtman Z et al. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expression and antitumor activity. Proc Natl Acad Sci U S A 2000 97 : 2573 8.
Rossignol M, Gagnon M, Klagsbrun M. Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms. Genomics 2000 70 : 211 22.
Hern S, Mortimer P. In vivo quantification of microvessels in clinically uninvolved psoriatic skin and in normal skin. Br J Dermatol 2007 156 : 1224 9.
Kunstfeld R, Hirakawa S, Hong YK et al. Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia. Blood 2004 104 : 1048 57.
Wu YY, Rees JL. Variation in epidermal housekeeping gene expression in different pathological states. Acta Derm Venereol (Stockh) 2000 80 : 2 3.
Trembath RC, Clough RL, Rosbotham JL et al. Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum Mol Genet 1997 6 : 813 20.
Young H, Summers A, Bhushan M et al. Single-nucleotide polymorphisms of vascular endothelial growth factor in psoriasis of early onset. J Invest Dermatol 2004 122 : 209 15.
Mamluk R, Klagsburn M, Detmar M et al. Soluble neuropilin targeted to the skin inhibits vascular permeability. Angiogenesis 2005 8 : 217 27.
Man XY, Yang XH, Cai SQ et al. Immunolocalization and expression of vascular endothelial growth factor receptors (VEGFRs) and neuropilins (NRPs) on keratinocytes in human epidermis. Mol Med 2006 12 : 127 36.
Schacht V, Dadras S, Johnson L et al. Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. Am J Pathol 2005 166 : 913 21.
Kapur N, Sahoo P, Wong AKC. A new method for gray-level picture thresholding using the entropy of the histogram. Comput Vis Graph Image Process 1985 29 : 273 85.
Soille P. Morphological Image Analysis: Principles and Applications. Berlin : Springer-Verlag, 1999 35 8.