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第 10 回日本-中国合同皮膚科学術会議 演 題 申 込 書 Title (English) 発表者と共同演者(発表者にはチェックをつけてください。 ) First name Family name Institution (English) □ (English) □ (English) □ (English) □ (English) □ (English) □ Correspondence Name Address Phone FAX E-mail Presentation type □Oral presentation □Poster (Final decision will be made by the program committee) □CPC Category (please mark topics best describing your presentation) □Appendages' Diseases □Bacterial and Viral Infection □Basic Research □Benign and Malignant Tumors □Bullous Diseases □Collagen Diseases and Vasculitis □Cosmetic Dermatology □Dermatitis and Skin Allergy □Fungal Infection □Genetic Disorders □Metabolic and Endocrine Disorders □Photodermatoses □Pigmentary Disorders □Psoriasis □Sexually Transmitted Diseases □Therapies □Miscellaneous 見本1 Bone morphogenetic protein-2 modulates Wnt and frizzled expression and upregulates Wnt-beta-catenin signaling pathway in normal keratinocytes Lujun YANG1, Kenshi YAMASAKI1, Yuji SHIRAKATA1, 2, Xiuju DAI1, Sho TOKUMARU1, and Koji HASHIMOTO1. 1 Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan 2 Center for Regenerative Medicine, Ehime University Graduate School of Medicine, Ehime, Japan Background: Bone morphogenetic protein-2 (BMP-2) and Wnt are involved in the development of skin and skin appendages as a morphogen. However, if there is crosstalk between BMP-2 and the Wnt/β-catenin signaling pathway is not clear. Objective: We examined BMP-2-dependent expression of Wnt and its receptor frizzled in normal human keratinocytes. Methods: The mRNA expression of the Wnt and frizzled families was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) or ribonuclease protection assay. β-Catenin expression was measured using RT-PCR and Western blotting. TCF/LEF activity was analyzed using the luciferase reporter assay. Results: We detected the expression of Wnt-2b/13, -4, -5a, -5b, -7a, -7b, and -10a, frizzled-1, -4, -5, -6, -8, -9, and -10, MFRP, and SFRP-1/SARP-2 in keratinocytes. BMP-2 increased Wnt-2b/13, -5b, and -7b, and frizzled-6, -8, and -10. Conversely, BMP-2 suppressed Wnt-10a and SFRP-1/SARP-2. Although Wnt-4 expression was not affected by BMP-2 in confluent conditioned keratinocytes, BMP-2 suppressed cell density-dependent Wnt-4 induction. The transcriptional activity of T-cell factor/lymphoid enhancing factor (TCF/LEF), which is a target of the canonical Wnt pathway, was upregulated by BMP-2 in both time- and dose-dependent manners. However, BMP-2-dependent differentiation of keratinocytes suppressed TCF/LEF transcriptional activity. Conclusion: These results suggest that BMP-2 modulates the expression of molecules involved in Wnt signaling, and activates the canonical Wnt pathway in normal human keratinocytes. Moreover, Wnt signaling may be influenced by the fate of keratinocytes, such as proliferation, migration, and differentiation. 見本2 Capillary leak syndrome complicating generalized pustular psoriasis: possible role of circulating vascular endothelial growth factor Yukiko INOUE, Yuji SHIRAKATA, Koji HASHIMOTO Department of Dermatology, Ehime University Graduate School of Medical Science, Ehime, Japan Introduction: Capillary Leak Syndrome was first described in 1960 by Clarkson et al and characterized by chronic recurrent episodes of a triad of hypotension, hypoalbuminemia and hemoconcentration. It is caused by increased capillary permeability and consists of the shift of fluid and proteins from the intravascular to the extra vascular compartment with subsequent hypovolemic shock. We report a case of Capillary Leak Syndrome accompanied with Generalized Pustular Psoriasis. Case Report: A 55-year old man, who had been diagnosed as Generalized Pustular Psoriasis for 25 years, admitted urgently with acute cardio respiratory failure and renal failure .He had developed pustular eruption on his trunk accompanied by generalized edema. He presented hypotension, anorexia, oliguria, high fever and disturbance of consciousness. Laboratory investigations revealed leukocytosis, (32000/l), an increase in both hematocrit (54%) and hemoglobin (17.4 g/dl), and decrease in albumin (2.9 g/dl) .Liver and renal function was also abnormal. His chest radiograph showed extensive bilateral alveolar shadowing consistent with profound pulmonary edema, which suggested capillary leak syndrome. He was transferred to the intensive care unit where he was provided ventilator support and continuous hemodiafiltration and treated with intravenous fluids, dopamine, albumin, predonisolone 60 mg/day and etretinate 50 mg/day. Three weeks later he recovered enough to quit mechanical ventilation and continuous hemodiafiltration. Comment: We diagnosed our present case as Capillary Leak Syndrome accompanied with Generalized Pustular Psoriasis, because it showed hypotension, hypoalbuminemia, hemoconcentration, generalized edema and renal failure. In 1994, Detmar et al reported that psoriatic skin express strikingly high amounts of vascular endothelial growth factor (VEGF). In 2002, Creamer indicated that patients with severe psoriasis (PASI score>30, Generalized Pustular Psoriasis) had significantly higher levels of plasma VEGF compared with patients with moderate psoriasis (PASI score<30). Therefore, we measured the concentration of plasma VEGF. On day 3 the concentration of VEGF was 1840.0 pg/ml and it was 77.2 pg/ml on day 20. Creamer et al suggest that VEGF entered the systemic circulation and acts on micro vessels to mediate hyper permeability. We suppose that high level of VEGF in early phase of Generalized Pustular Psoriasis is associated with a case of Capillary Leak Syndrome. Capillary Leak Syndrome is known as severe disorder with a high mortality rate. We suggest that there is some possibility of predicting the onset of Capillary Leak Syndrome by measuring of the plasma VEGF in patients with Generalized Pustular Psoriasis.