Disruption of TGF-beta signaling in smooth muscle cell prevents elastase-induced abdominal aortic aneurysm.
Fiche publication
Date publication
novembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Gao F, Chambon P, Offermanns S, Tellides G, Kong W, Zhang X, Li W
Lien Pubmed
Résumé
Transforming growth factor-beta (TGF-beta) signaling has been significantly implicated in the pathogenesis of aneurysm, prominently the initiation and progression of abdominal aortic aneurysm (AAA). Vascular smooth muscle cell (SMC) is the principal resident cell in aortic wall and is essential for its structure and function. However, the role of TGF-beta pathway in SMC for the formation of AAA remains unknown. Therefore, the goal of the present study was to investigate the effect of TGF-beta pathway in SMC for AAA pathogenesis, by using a genetical smooth muscle-specific (SM-specific) TGF-beta type II receptor (Tgfbr2) disruption animal model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2(f/f) and MyhCre.Tgfbr2(WT/f)) and their corresponding wild-type background mice (MyhCre.Tgfbr2(WT/WT)) underwent AAA induction by infrarenal peri-adventitial application of elastase. Fourteen days after elastase treatment, the aortas were analyzed and indicated that disruption of 1 or 2 alleles of Tgfbr2 in SMC provided markedly step-wise protection from AAA formation. And elastin degradation, medial SMC loss, macrophage infiltration, and matrix metalloproteinases (MMP) expression were all significantly reduced in Tgfbr2 deletion mice. Our study demonstrated, for the first time, that the TGF-beta signaling pathway in SMC plays a critical role in AAA and disruption can prevent the aneurysm formation.
Référence
Biochem Biophys Res Commun. 2014 Nov 7;454(1):137-43