Document Detail


JNK is critical for the development of Candida albicans-induced vascular lesions in a mouse model of Kawasaki Disease.
MedLine Citation:
PMID:  25242023     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Kawasaki disease (KD) is the most common systemic vasculitis of unknown etiology in children, and can cause the life-threatening complication of coronary artery aneurysm. Although a novel treatment strategy for patients with KD-caused vascular lesions is eagerly awaited, their molecular pathogenesis remains largely unknown. c-Jun N-terminal kinase (JNK) is a signaling molecule known to have roles in inflammation and tissue remodeling. The aim of this study was to elucidate significant involvement of JNK in the development of vascular lesions in a mouse model of KD.
METHODS AND RESULTS: We injected Candida albicans cell wall extract (CAWE) into 4-week-old C57BL/6 mice. Macroscopically, we found that CAWE caused the development of bulging lesions at coronary artery, carotid artery, celiac artery, iliac artery and abdominal aorta. Histological examination of coronary artery and abdominal aorta in CAWE-treated mice showed marked inflammatory cell infiltration, destruction of elastic lamellae, loss of medial smooth muscle cells and intimal thickening, which are similar to histological features of vascular lesions of patients with KD. To find the role of JNK in lesion formation, we evaluated the effects of JNK inhibitor, SP600125, on abdominal aortic lesions induced by CAWE. Interestingly, treatment with SP600125 significantly decreased the incidence of lesions and also protected against vascular inflammation and tissue destruction histologically, compared with the placebo treatment.
CONCLUSIONS: Our findings suggest that JNK is crucial for the development of CAWE-induced vascular lesions in mice, and potentially represents a novel therapeutic target for KD.
Authors:
Yukako Yoshikane; Mitsuhisa Koga; Kyoko Imanaka-Yoshida; Tamaki Cho; Yumi Yamamoto; Toshimichi Yoshida; Junichi Hashimoto; Shinichi Hirose; Koichi Yoshimura
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-28
Journal Detail:
Title:  Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology     Volume:  -     ISSN:  1879-1336     ISO Abbreviation:  Cardiovasc. Pathol.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-9-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9212060     Medline TA:  Cardiovasc Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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