638 251

Cited 0 times in

The effect of corticosteroid on the acantholysis induced by pemphigus vulgaris IgG

DC FieldValueLanguage
dc.contributor.author장재용-
dc.date.accessioned2015-12-24T09:49:32Z-
dc.date.available2015-12-24T09:49:32Z-
dc.date.issued2014-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/136658-
dc.descriptionDept. of Medicine/박사-
dc.description.abstractPemphigus vulgaris (PV) is a potentially fatal blistering disease characterized by autoantibodies against the desmosomal adhesion protein desmoglein (Dsg) 3. It has been proven that autoantibodies against Dsg 3 cause loss of cell-cell adhesion (acantholysis) which is pathognomic histologic finding in PV. Although the pathomechanism of acantholysis still remains unclear, one explanation is that an antibody binding to Dsg extracellular domain simply blocks adhesion by steric hindrance. However, PV pathogenesis involves more than steric hindrance. Recently, increasing evidences showed that variety of intracellular signaling pathways are also involved in the loss of cell-cell adhesion.Several signaling pathways have been introduced. First, p38 mitogen-activated protein kinase (p38 MAPK) activation, which is necessary for blister formation in response to PV IgG, leads to endocytosis of multiple desmosomal molecules. Second, activation of c-myc and epidermal growth factor receptor (EGFR) can also cause blister formation in PV. Third, PV IgG results endocytosis of Dsg3 by using adhesion-signaling network binding to Dsgs. Fourth, hyperproliferation can lead to acantholysis by unknown mechanisms. Blocking PV IgG induced intracellular signaling and Dsg3 endocytosis or Dsg3 exogenous expression may prevent acantholysis in response to PV IgG.Corticosteroid is still mainstay of treatment in PV, however, the precise therapeutic role of corticosteroid in PV IgG induced acantholysis has not yet been elucidated. In this study, the effects of corticosteroid on the process of PV IgG induced acnatholysis were investigated.Dexamethasone attenuated PV IgG induced loss of keratinocyte adhesion in dissociation-based assay. Dexamethasone attenuated PV IgG induced Dsg endocytosis and depletion in immunofluorescence examination of cultured keratinocytes. Immunoblot analysis revealed that the protein level of Dsg3 decreased rapidly until 12 hr incubation at 37℃ with PV IgG and that the decrease of Dsg3 was delayed by dexamethasone. Phosphorylated p38 was increased in dual peaks after 1 hr and 12-24 hrs of incubation with PV IgG, whereas phosphorylated p38 was decreased in the early phase after incubation with PV IgG and dexamethasone. Phosphorylated ERK was increased in peak after 30 mins of incubation with PV IgG. However, elevated peak of phosphorylated ERK was not observed with PV IgG and dexamethasone.Therefore, this study suggests that corticosteroid plays an important role on the blocking of PV IgG induced acantholysis through attenuating depletion of Dsg3 and phosphorylation of p38 MAPK and ERK signaling.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.publisherGraduate School, Yonsei University-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleThe effect of corticosteroid on the acantholysis induced by pemphigus vulgaris IgG-
dc.title.alternative보통 천포창 환자의 면역글로불린 G에 의해 유도된 가시세포분리에 스테로이드가 미치는 영향-
dc.typeThesis-
dc.contributor.alternativeNameChang, Jae Yong-
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 3. Dissertation

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.