Molecular function and signaling in regulation of desmosomal adhesion : effects of pemphigus IgG

天疱疮（Pemphigus， P）是一种自身免疫性大疱性疾病，由抗桥粒黏附分子的自身抗体引起的桥粒破坏引起，普通天疱疮（pemphigis， PV）的桥粒蛋白3 （Dsg3）或pemphigis的Dsg1。叶青（PF）。目前尚不清楚PV-IgG与粘粒蛋白结合后是如何引起水疱的。本研究的目的是从PV-IgG结合引起的外向内信号传导和控制桥粒粘连的角度阐明PV-IgG诱导水泡的机制。我们之前已经证明PV-IgG可以激活蛋白激酶C，介导纤溶酶原激活剂（uPA）的分泌、uPA受体（uPAR）的表达以及Dsg3的磷酸化，Dsg3的降解和与血小板红蛋白的分离有关。在本研究中，我们通过使用uPAR抑制剂的抑制实验揭示了uPAR在起泡中的作用（Gun Exp Dermatol 26: 289-295, 2001），并证明pv - igg结合不会引起桥粒粘附的位阻（J Invest Dermatol 117: 406, 2001）。此外，我们发现在Dsg3-ELISA滴度降至正常范围之前，临床症状就消失了（the 23^<rd> the Annual Meeting of blous Disease Research Club, 2003）。我们还介绍了PV-IgG对其他桥粒分子（桥粒素，桥粒蛋白）的影响的实验结果。皮肤实验27:684-690,2002，皮肤实验295:s17- 123,2003)，并研究了乙酰胆碱受体在角质形成细胞细胞粘附中的作用（生命科学72:208 -2085,2003,Exp Cell Res 2004, in press）。最近，我们发表了新的研究结果，PV-IgG和methylprednisoline对角质形成细胞具有相互作用（J Biol Chem279: 2132-2146, 2004）。关于角蛋白细胞骨架和大疱性表皮松解症，我们发现了两种新的突变类型和一种新的临床类型，这是由一种新的帧移位和延迟终止密码子突变引起的（J Dermatol 29: 136- 145,2002; J Invest Dermatol 121: 482-485, 2003）。

Pemphigus (P) is an autoimmune bullous disease caused by disruption of desmosomes due to autoantibodies against desmosomal adhesion molecules, desmoglein 3 (Dsg3) for P vulgaris (PV) or Dsg1 for. P foliaceus (PF). It is yet unknown how blisters are induced after PV-IgG bound to desmogleins. The aim of this study is to elucidate the mechanisms of PV-IgG-induced blistering in terms of outside-in signaling caused by PV-IgG binding and control desmosome adhesion. We have previously showed that PV-IgG causes activation of protein kinase C, mediating the secretion of plasminogen activator (uPA), expression of uPA receptor (uPAR), and phosphorylation of Dsg3 associated with its degradation and dissociation from plakoglobin. In the present study, we revealed the involvement of uPAR in blistering by inhibition experiments using uPAR inhibitors (Gun Exp Dermatol 26: 289-295, 2001), and demonstrated that PV-IgG-binding did not cause steric hindrance of desmosome adhesion (J Invest Dermatol 117: 406, 2001). In addition, we showed that clinical symptoms disappear before the titers of Dsg3-ELISA decreased down to normal range (The 23^<rd> Annual Meeting of Bullous Disease Research Club, 2003). We also presented experimental results on the effects of PV-IgG on the other desmosomal molecules (desmocollins, desmoplakins) (Clin.Exp Dermatol 27 : 684-690, 2002, Arch Dermatol Res 295 : s17-123, 2003), and showed the involvement of acetylcholine receptor function in cell-cell adhesion in keratinocytes (Life Science 72 : 208 1-2085, 2003, Exp Cell Res 2004, in press). Recently, we published new results that PV-IgG and methylprednisoline exhibit reciprocal effects on keratinocytes (J Biol Chem279 : 2132-2146, 2004). Regarding the keratin cytoskeleton and epidermolysis bullosa, we found two new types of mutation and a new clinical type of this diseases caused by a new frame-shift and delayed termination codon mutation (J Dermatol 29 : 136-145, 2002, J Invest Dermatol 121: 482-485, 2003).