Systematic name M1885
Brief description Genes down-regulated in vascular smooth muscle cells (VSMC) by MAPK8 (JNK1) [GeneID=5599].
Full description or abstract Abdominal aortic aneurysm (AAA) is a common disease among elderly people that, when surgical treatment is inapplicable, results in progressive expansion and rupture of the aorta with high mortality. Although nonsurgical treatment for AAA is much awaited, few options are available because its molecular pathogenesis remains elusive. Here, we identify JNK as a proximal signaling molecule in the pathogenesis of AAA. Human AAA tissue showed a high level of phosphorylated JNK. We show that JNK programs a gene expression pattern in different cell types that cooperatively enhances the degradation of the extracellular matrix while suppressing biosynthetic enzymes of the extracellular matrix. Selective inhibition of JNK in vivo not only prevented the development of AAA but also caused regression of established AAA in two mouse models. Thus, JNK promotes abnormal extracellular matrix metabolism in the tissue of AAA and may represent a therapeutic target.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16311603   Authors: Yoshimura K,Aoki H,Ikeda Y,Fujii K,Akiyama N,Furutani A,Hoshii Y,Tanaka N,Ricci R,Ishihara T,Esato K,Hamano K,Matsuzaki M
Exact source Table 1S: J.I. < 0
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Source species Rattus norvegicus
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Version history 3.1: First introduced

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