Fibroblast growth factor receptor 2 gene codes for IIIb and IIIc transcript variants, which play pivotal roles in normal wound healing. Tumor necrosis factor α mediates several biological processes including wound healing. We aimed to characterise the expression pattern of IIIb expressed by in vitro cultured keratinocytes and in skin biopsy samples of venous leg ulcer patients, and to identify polymorphisms which may play a role in the pathomechanism of prolonged wound healing in venous leg ulcer patients. Real-time reverse transcription polymerase chain reaction and Western blotting methods were used for expression studies, polymerase chain reaction with TaqMan probes and with restriction fragment length polymorphism method were performed for polymorphism studies. We demonstrated that the expression of IIIb is related to the proliferation states of HaCaT keratinocytes and its expression is down-regulated in the uninvolved epidermis of venous leg ulcer patients ( n = 15) compared to the epidermis of controls ( n = 15). We identified a polymorphism in the 3’ untranslated region (2451A/G) of the fibroblast growth factor receptor 2 gene, which displayed a significant difference in the allelic distribution between leg ulcer patients ( n = 82) and controls ( n = 82; p = 0.0103). We hypothesize that this polymorphism may be a susceptibility factor for venous leg ulcer. In another set of experiment we demonstrated that the A allele of the –308 tumor necrosis factor α polymorphism might be a potential factor for venous leg ulcer susceptibility; however, our data suggest that this association is secondary and the primary association probably exists with obesity.
-
Stucker, M., Harke, K., Rudolph, T. et al.: Pathogenesis of therapy refractory ulcus cruris. Hautarzt., 2003, 54 , 750–755.
Rudolph T. , 'Pathogenesis of therapy refractory ulcus cruris ' (2003 ) 54 Hautarzt. : 750 -755 .
-
Jawien, A.: The influence of environmental factors in chronic venous insufficiency. Angiology., 2003, 1 , S19–31.
Jawien A. , 'The influence of environmental factors in chronic venous insufficiency ' (2003 ) 1 Angiology. : S19 -31 .
-
Munkvad, S., Jorgensen, M.: Resistance to activated protein C: A common anticoagulant deficiency in patients with venous leg ulceration. J. Dermatol., 1996, 134 , 296–298.
Jorgensen M. , 'Resistance to activated protein C: A common anticoagulant deficiency in patients with venous leg ulceration ' (1996 ) 134 J. Dermatol. : 296 -298 .
-
Kim, B. C., Kim, H. T., Park, S. H. et al.: Fibroblasts from chronic wounds show altered TGF-beta-signaling and decreased TGF-beta Type II receptor expression. J. Cell. Physiol., 2003, 195 , 331–336.
Park S. H. , 'Fibroblasts from chronic wounds show altered TGF-beta-signaling and decreased TGF-beta Type II receptor expression ' (2003 ) 195 J. Cell. Physiol. : 331 -336 .
-
Toumi, H., F’guyer, S., Best, T. M.: The role of neutrophils in injury and repair following muscle stretch. J. Anat., 2006, 208 , 459–470.
Best T. M. , 'The role of neutrophils in injury and repair following muscle stretch ' (2006 ) 208 J. Anat. : 459 -470 .
-
Werner, S., Smola, H., Liao, X. et al.: The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science, 1994, 266 , 819–822.
Liao X. , 'The function of KGF in morphogenesis of epithelium and reepithelialization of wounds ' (1994 ) 266 Science : 819 -822 .
-
Singer, A. J., Clark, R. A.: Cutaneous wound healing. N. Engl. J. Med., 1999, 341 , 738–746.
Clark R. A. , 'Cutaneous wound healing ' (1999 ) 341 N. Engl. J. Med. : 738 -746 .
-
Dipietro, L. A., Reintjes, M. G., Low, Q. E. et al.: Modulation of macrophage recruitment into wounds by monocyte chemoattractant protein-1. Wound Repair Regen., 2001, 9 , 28–33.
Low Q. E. , 'Modulation of macrophage recruitment into wounds by monocyte chemoattractant protein-1 ' (2001 ) 9 Wound Repair Regen. : 28 -33 .
-
Nissen, N. N., Polverini, P. J., Koch, A. E. et al.: Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am. J. Pathol., 1998, 152 , 1445–1452.
Koch A. E. , 'Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing ' (1998 ) 152 Am. J. Pathol. : 1445 -1452 .
-
Laurens, N., Koolwijk, P., de Maat, M. P.: Fibrin structure and wound healing. J. Thromb. Haemost., 2006, 4 , 932–939.
Maat M. P. , 'Fibrin structure and wound healing ' (2006 ) 4 J. Thromb. Haemost. : 932 -939 .
-
Holmbeck, K., Szabova, L.: Aspects of extracellular matrix remodeling in development and disease. Birth. Defects. Res. C. Embryo Today, 2006, 78 , 11–23.
Szabova L. , 'Aspects of extracellular matrix remodeling in development and disease ' (2006 ) 78 Birth. Defects. Res. C. Embryo Today : 11 -23 .
-
Zhang, Y., Gorry, M. C., Post, J. C. et al.: Genomic organization of the human fibroblast growth factor receptor 2 (FGFR2) gene and comparative analysis of the human FGFR gene family. Gene, 1999, 230 , 69–79.
Post J. C. , 'Genomic organization of the human fibroblast growth factor receptor 2 (FGFR2) gene and comparative analysis of the human FGFR gene family ' (1999 ) 230 Gene : 69 -79 .
-
Twigg, S. R., Burns, H. D., Oldridge, M. et al.: Conserved use of a non-canonical 5’ splice site (/GA) in alternative splicing by fibroblast growth factor receptors 1, 2 and 3. Hum. Mol. Genet., 1998, 7 , 685–691.
Oldridge M. , 'Conserved use of a non-canonical 5’ splice site (/GA) in alternative splicing by fibroblast growth factor receptors 1, 2 and 3 ' (1998 ) 7 Hum. Mol. Genet. : 685 -691 .
-
Ingersoll, R. G., Paznekas, W. A., Tran, A. K. et al.: Fibroblast growth factor receptor 2 (FGFR2): genomic sequence and variations. Cytogenet. Cell Genet., 2001, 94 , 121–126.
Tran A. K. , 'Fibroblast growth factor receptor 2 (FGFR2): genomic sequence and variations ' (2001 ) 94 Cytogenet. Cell Genet. : 121 -126 .
-
Finch, P. W., Murphy, F., Cardinale, I. et al.: Altered expression of keratinocyte growth factor and its receptor in psoriasis. Am. J. Pathol., 1997, 151 , 1619–1628.
Cardinale I. , 'Altered expression of keratinocyte growth factor and its receptor in psoriasis ' (1997 ) 151 Am. J. Pathol. : 1619 -1628 .
-
Reardon, W., Winter, R. M., Rutland, P. et al.: Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nature Genetics, 1994, 8 , 98–103.
Rutland P. , 'Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome ' (1994 ) 8 Nature Genetics : 98 -103 .
-
Fujisawa, H., Hasegawa, M., Kida, S. et al.: A novel fibroblast growth factor receptor 2 mutation in Crouzon syndrome associated with Chiari type 1 malformation and syringomyelia. J. Neurosurg., 2002, 97 , 396–400.
Kida S. , 'A novel fibroblast growth factor receptor 2 mutation in Crouzon syndrome associated with Chiari type 1 malformation and syringomyelia ' (2002 ) 97 J. Neurosurg. : 396 -400 .
-
Nedwin, G. E., Svedersky, L. P., Bringman, T. S. et al.: Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J. Immunol., 1985, 135 , 2492–2497.
Bringman T. S. , 'Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta ' (1985 ) 135 J. Immunol. : 2492 -2497 .
-
Black, R. A., Rauch, C. T., Kozlosky, C. J. et al.: A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature, 1997, 385 , 729–733.
Kozlosky C. J. , 'A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells ' (1997 ) 385 Nature : 729 -733 .
-
Hoffman, M., Cooper, S. T.: Thrombin enhances monocyte secretion of tumor necrosis factor and interleukin-1 beta by two distinct mechanisms. Blood Cells Mol. Dis., 1995, 21 , 156–167.
Cooper S. T. , 'Thrombin enhances monocyte secretion of tumor necrosis factor and interleukin-1 beta by two distinct mechanisms ' (1995 ) 21 Blood Cells Mol. Dis. : 156 -167 .
-
Hotamisligil, G. S., Peraldi, P., Budavari, A. et al.: IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science, 1996, 271 , 665–668.
Budavari A. , 'IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance ' (1996 ) 271 Science : 665 -668 .
-
Crist, S. A., Elzey, B. D., Ludwig, A. T. et al.: Expression of TNF-related apoptosis-inducing ligand (TRAIL) in megakaryocytes and platelets. Exp. Hematol., 2004, 32 , 1073–1081.
Ludwig A. T. , 'Expression of TNF-related apoptosis-inducing ligand (TRAIL) in megakaryocytes and platelets ' (2004 ) 32 Exp. Hematol. : 1073 -1081 .
-
Wallace, H. J., Stacey, M. C.: Levels of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in chronic venous leg ulcers–correlations to healing status. J. Invest. Dermatol., 1988, 110 , 292–296.
Stacey M. C. , 'Levels of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in chronic venous leg ulcers–correlations to healing status ' (1988 ) 110 J. Invest. Dermatol. : 292 -296 .
-
Streit, M., Beleznay, Z., Braathen, L. R.: Topical application of the tumour necrosis factor-alpha antibody infliximab improves healing of chronic wounds. Int. Wound J., 2006, 3 , 171–179.
Braathen L. R. , 'Topical application of the tumour necrosis factor-alpha antibody infliximab improves healing of chronic wounds ' (2006 ) 3 Int. Wound J. : 171 -179 .
-
Higuchi, T., Seki, N., Kamizono, S. et al.: Polymorphism of the 5’-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese. Tissue Antigens, 1998, 51 , 605–612.
Kamizono S. , 'Polymorphism of the 5’-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese ' (1998 ) 51 Tissue Antigens : 605 -612 .
-
McGuire, W., Hill, A. V. S., Allsopp, C. E. M. et al.: Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature, 1994, 371 , 508–511.
Allsopp C. E. M. , 'Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria ' (1994 ) 371 Nature : 508 -511 .
-
Moffatt, M. F., Cookson, W. O. C. M.: Tumour necrosis factor haplotypes and asthma. Hum. Molec. Genet., 1997, 6 , 551–554.
Cookson W. O. C. M. , 'Tumour necrosis factor haplotypes and asthma ' (1997 ) 6 Hum. Molec. Genet. : 551 -554 .
-
Sashio, H., Tamura, K., Ito, R. et al.: Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn’s disease, respectively. Immunogenetics, 2002, 53 , 1020–1027.
Ito R. , 'Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn’s disease, respectively ' (2002 ) 53 Immunogenetics : 1020 -1027 .
-
Wallace, H. J., Vandongen, Y. K., Stacey, M. C.: Tumor necrosis factor-alpha gene polymorphism associated with increased susceptibility to venous leg ulceration. J. Invest. Dermatol., 2006, 126 , 921–925.
Stacey M. C. , 'Tumor necrosis factor-alpha gene polymorphism associated with increased susceptibility to venous leg ulceration ' (2006 ) 126 J. Invest. Dermatol. : 921 -925 .
-
Hoffstedt, J., Eriksson, P., Hellstrom, L. et al.: Excessive fat accumulation is associated with the TNF alpha-308 G/A promoter polymorphism in women but not in men. Diabetologia, 2002, 43 , 117–120.
Hellstrom L. , 'Excessive fat accumulation is associated with the TNF alpha-308 G/A promoter polymorphism in women but not in men ' (2002 ) 43 Diabetologia : 117 -120 .
-
Brand, E., Schorr, U., Kunz, I. et al.: Tumor necrosis factor-alpha –308 G/A polymorphism in obese Caucasians. Int. J. Obes. Relat. Metab. Disord., 2001, 25 , 581–585.
Kunz I. , 'Tumor necrosis factor-alpha –308 G/A polymorphism in obese Caucasians ' (2001 ) 25 Int. J. Obes. Relat. Metab. Disord. : 581 -585 .
-
Walston, J., Seibert, M., Yen, C. J. et al.: Tumor necrosis factor-alpha –238 and –308 polymorphisms do not associate with traits related to obesity and insulin resistance. Diabetes, 1999, 48 , 2096–2098.
Yen C. J. , 'Tumor necrosis factor-alpha –238 and –308 polymorphisms do not associate with traits related to obesity and insulin resistance ' (1999 ) 48 Diabetes : 2096 -2098 .
-
Maas-Szabowski, N., Szabowski, A., Stark, H. J. et al.: Organotypic cocultures with genetically modified mouse fibroblasts as a tool to dissect molecular mechanisms regulating keratinocyte growth and differentiation. J. Invest. Dermatol., 2001, 116 , 816–820.
Stark H. J. , 'Organotypic cocultures with genetically modified mouse fibroblasts as a tool to dissect molecular mechanisms regulating keratinocyte growth and differentiation ' (2001 ) 116 J. Invest. Dermatol. : 816 -820 .
-
Marchese, C., Sorice, M., De Stefano, C. et al.: Modulation of keratinocyte growth factor receptor expression in human cultured keratinocytes. Cell. Growth. Differ., 1997, 8 , 989–997.
Stefano C. , 'Modulation of keratinocyte growth factor receptor expression in human cultured keratinocytes ' (1997 ) 8 Cell. Growth. Differ. : 989 -997 .
-
Capone, A., Visco, V., Belleudi, F. et al.: Up-modulation of the expression of functional keratinocyte growth factor receptors induced by high cell density in the human keratinocyte HaCaT cell line. Cell. Growth. Differ., 2000, 11 , 607–614.
Belleudi F. , 'Up-modulation of the expression of functional keratinocyte growth factor receptors induced by high cell density in the human keratinocyte HaCaT cell line ' (2000 ) 11 Cell. Growth. Differ. : 607 -614 .
-
Visco, V., Belleudi, F., Marchese, C. et al.: Differential response to keratinocyte growth factor receptor and epidermal growth factor receptor ligands of proliferating and differentiating intestinal epithelial cells. J. Cell. Physiol., 2004, 200 , 31–44.
Marchese C. , 'Differential response to keratinocyte growth factor receptor and epidermal growth factor receptor ligands of proliferating and differentiating intestinal epithelial cells ' (2004 ) 200 J. Cell. Physiol. : 31 -44 .
-
Marchese, C., Visco, V., Aimati, L. et al.: Nickel-induced keratinocyte proliferation and up-modulation of the keratinocyte growth factor receptor expression. Exp. Dermatol., 2003, 12 , 497–505.
Aimati L. , 'Nickel-induced keratinocyte proliferation and up-modulation of the keratinocyte growth factor receptor expression ' (2003 ) 12 Exp. Dermatol. : 497 -505 .
-
Pivarcsi, A., Szell, M., Kemeny, L. et al.: Serum factors regulate the expression of the proliferation-related genes alpha5 integrin and keratin 1, but not keratin 10, in HaCaT keratinocytes. Arch. Dermatol. Res., 2001, 293 , 206–213.
Kemeny L. , 'Serum factors regulate the expression of the proliferation-related genes alpha5 integrin and keratin 1, but not keratin 10, in HaCaT keratinocytes ' (2001 ) 293 Arch. Dermatol. Res. : 206 -213 .
-
Woodcock-Mitchell, J., Eichner, R., Nelson, W. G. et al.: Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J. Cell. Biol., 1982, 95 , 80–588.
Nelson W. G. , 'Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies ' (1982 ) 95 J. Cell. Biol. : 80 -588 .
-
Cancello, R., Tounian, A., Poitou, C. H. et al.: Adiposity signals, genetic and body weight regulation in humans. Diabetes. Metab., 2004, 30 , 215–227.
Poitou C. H. , 'Adiposity signals, genetic and body weight regulation in humans ' (2004 ) 30 Diabetes. Metab. : 215 -227 .
-
Marchese, C., Rubin, J., Ron, D. et al.: Human keratinocyte growth factor activity on proliferation and differentiation of human keratinocytes: differentiation response distinguishes KGF from EGF family. J. Cell. Physiol., 1990, 144 , 326–332.
Ron D. , 'Human keratinocyte growth factor activity on proliferation and differentiation of human keratinocytes: differentiation response distinguishes KGF from EGF family ' (1990 ) 144 J. Cell. Physiol. : 326 -332 .
-
Kemeny, L., Gross, E., Arenberger, P. et al.: Dithranol-induced down-regulation of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] receptors in a human epidermal cell line. Arch. Dermatol. Res., 1991, 283 , 333–336.
Arenberger P. , 'Dithranol-induced down-regulation of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] receptors in a human epidermal cell line ' (1991 ) 283 Arch. Dermatol. Res. : 333 -336 .
-
Pol, A., Bergers, M., Schalkwijk, J.: Comparison of antiproliferative effects of experimental and established antipsoriatic drugs on human keratinocytes, using a simple 96-well-plate assay. In Vitro Cell. Dev. Biol. Anim., 2003, 39 , 36–42.
Schalkwijk J. , 'Comparison of antiproliferative effects of experimental and established antipsoriatic drugs on human keratinocytes, using a simple 96-well-plate assay ' (2003 ) 39 In Vitro Cell. Dev. Biol. Anim. : 36 -42 .
-
Kemeny, L., Ruzicka, T., Braun-Falco, O.: Dithranol: a review of the mechanism of action in the treatment of psoriasis vulgaris. Skin. Pharmacol., 1990, 3 , 1–20.
Braun-Falco O. , 'Dithranol: a review of the mechanism of action in the treatment of psoriasis vulgaris ' (1990 ) 3 Skin. Pharmacol. : 1 -20 .
-
Kemeny, L., Michel, G., Arenberger, P. et al.: Down-regulation of epidermal growth factor receptors by dithranol. Acta Derm. Venereol., 1993, 73 , 37–40.
Arenberger P. , 'Down-regulation of epidermal growth factor receptors by dithranol ' (1993 ) 73 Acta Derm. Venereol. : 37 -40 .
-
Farkas, A., Kemeny, L., Szony, B. J. et al.: Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell line HaCaT. Inflamm. Res., 2001, 50 , 44–49.
Szony B. J. , 'Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell line HaCaT ' (2001 ) 50 Inflamm. Res. : 44 -49 .
-
Hotchin, N. A., Kovach, N. L., Watt, F. M.: Functional down-regulation of alpha 5 beta 1 integrin in keratinocytes is reversible but commitment to terminal differentiation is not. J. Cell. Sci., 1993, 106 , 1131–1138.
Watt F. M. , 'Functional down-regulation of alpha 5 beta 1 integrin in keratinocytes is reversible but commitment to terminal differentiation is not ' (1993 ) 106 J. Cell. Sci. : 1131 -1138 .
-
Bretland, A. J., Lawry, J., Sharrard, R. M.: A study of death by anoikis in cultured epithelial cells. Cell. Prolif., 2001, 34 , 199–210.
Sharrard R. M. , 'A study of death by anoikis in cultured epithelial cells ' (2001 ) 34 Cell. Prolif. : 199 -210 .
-
Pedchenko, V. K., Imagawa, W. T.: Mammogenic hormones differentially modulate keratinocyte growth factor (KGF)-induced proliferation and KGF receptor expression in cultured mouse mammary gland epithelium. Endocrinology, 1998, 139 , 2519–2526.
Imagawa W. T. , 'Mammogenic hormones differentially modulate keratinocyte growth factor (KGF)-induced proliferation and KGF receptor expression in cultured mouse mammary gland epithelium ' (1998 ) 139 Endocrinology : 2519 -2526 .
-
Bata-Csorgo, Z., Hammerberg, C., Voorhees, J. J. et al.: Kinetics and regulation of human keratinocyte stem cell growth in short-term primary ex vivo culture. Cooperative growth factors from psoriatic lesional T lymphocytes stimulate proliferation among psoriatic uninvolved, but not normal, stem keratinocytes. J. Clin. Invest., 1995, 95 , 317–327.
Voorhees J. J. , 'Kinetics and regulation of human keratinocyte stem cell growth in short-term primary ex vivo culture. Cooperative growth factors from psoriatic lesional T lymphocytes stimulate proliferation among psoriatic uninvolved, but not normal, stem keratinocytes ' (1995 ) 95 J. Clin. Invest. : 317 -327 .
-
Raccah, D., Coste, T. C., Vague, P.: Genetics of diabetic complications: Peripheral neuropathy. Ann. Endocrinol., 2004, 65 , S5–S9.
Vague P. , 'Genetics of diabetic complications: Peripheral neuropathy ' (2004 ) 65 Ann. Endocrinol. : S5 -S9 .
| Hungarian Medical Journal | |
|---|---|
| Language | English |
| Size | |
| Year of Foundation |
2007 |
| Publication Programme |
ceased |
| Volumes per Year |
|
| Issues per Year |
|
| Publisher | Akadémiai Kiadó |
| Publisher's Address |
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245. |
| Responsible Publisher |
Chief Executive Officer, Akadémiai Kiadó |
| ISSN | 1788-6139 (Print) |
| ISSN | 1789-0403 (Online) |
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