TGF-β signaling in aortic aneurysm: another round of controversy

作     者：Fuyu Lin Xiao Yang 

作者机构：State Key Laboratory of Proteomics Genetic Laboratory of Development and Diseases Institute of Biotechnology Beijing 100071 China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2010年第37卷第9期

页      面：583-591页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 080801[工学-电机与电器] 081704[工学-应用化学] 0808[工学-电气工程] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

基　　金：supported by the grants from State Key Laboratory of Proteomics (No. SKLP-K200902) Chinese Key Program for Drug Invention (No. 2009ZX09501-027) Chinese National Key Program on Basic Research (Nos. 2005CB522506, 2006CB943501 and 2006BAI23B01-3) 

主　　题：aneurysm TGF-β signaling mouse model 

摘      要：Aortic aneurysm （AA） is a common health problem with high mortality and no effective drugs. Transforming growth factor-β （TGF-β） superfamily members regulate various cellular processes, and TGF-β signaling has key roles in development, tissue homeo- stasis, and diseases. Interest in the role of TGF-β signaling in the pathogenesis of AAs has recently emerged, particularly since genetic studies demonstrated an association between gene mutations in components of TGF-β signaling and AAs. However, paradoxical discoveries have implicated dysregulated TGF-β signaling in aneurysm formation, complicating the precise functional role for TGF-β in aneurysm development and progression. Furthermore, interventions targeting towards TGF-β signaling using losartan, which may represent a suitable therapeutic option for AAs, were subject to skepticism especially because of conflicting experimental results obtained from TGF-β antibody treatment without knowledge of the underlying mechanism. We propose a TGF-β aneurysm paradox, which would provide a good opportunity for the development of genetic mouse models of AA. These models would be used to clarify the mechanisms underlying TGF-β signaling, which would translate into novel pharmacologic therapies based on the new molecular discoveries.