Der Einfluss von N-Cadherin auf die Migration glatter Gefäßmuskelzellen im Rahmen der Restenoseentstehung

Objective: In this study we analyze the role of N-cadherin during human arterial smooth muscle cell (haSMC) migration and Rho-family GTPases-mediated dynamic rearrangement of cell–cell adhesion. Methods: Expression patterns of N-cadherin and beta-catenin were analyzed in vivo using a domestic pig restenosis model (expression after 14, 28, and 90 days) as well as in vitro by analysis of quiescent and migratory haSMCs. Upregulation of N-cadherin expression was induced by transient sense transfection whereas expression was downregulated by antisense transfection. For functional inhibition, antibody GC-4 was used. Quantification of cell migration was detected by Boyden chamber assays. Regulation of RhoA GTPase was tested by assessment of RhoA activity. Results: The analysis of N-cadherin expression in vivo by a porcine restenosis model revealed downregulation in the neointima after 14 days. After 28 days, N-cadherin expression was slightly restored, while after 90 days, no difference between medial and neointimal expression was detectable. During the whole period beta-catenin levels remained unchanged. According to these results the analysis in vitro showed a significant downregulation of N-cadherin in migratory haSMCs compared to quiescent cells. Overexpression of N-cadherin after transfection leaded to reduction of haSMC migration by 87% (P<0.001). By contrast, inhibition of N-cadherin in quiescent haSMCs by GC-4 increased the migratory potential by 87% (P<0.01). After N-cadherin overexpression in haSMCs RhoA activity was significantly upregulated while RhoA activity was blocked by GC-4. Conclusions: These results indicate that the regulation of haSMC attachment by N-cadherins is essential for haSMC migration. Modification of N-cadherin expression and activity induces RhoA signaling with relevance for the reorganization of the actin cytoskeleton.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Stein, Julia

Contributors dc:contributor

• Blindt, Rüdiger

• info:eu-repo/classification/ddc/610
• Adhäsionsproteine
• Restenose
• Gefäßmuskelzelle
• Medizin
• Adhesion molecules
• Restenosis
• Smooth muscle cells

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-112634%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50072