Wang JuFang, Tomar Dhadendra, Martin Thomas G, Dubey Shubham, Dubey Praveen K, Song Jianliang, Landesberg Gavin, McCormick Michael G, Myers Valerie D, Merali Salim, Merali Carmen, Lemster Bonnie, McTiernan Charles F, Khalili Kamel, Madesh Muniswamy, Cheung Joseph Y, Kirk Jonathan A, Feldman Arthur M
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.
Center for Neurovirology and Gene Editing, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.
JACC Basic Transl Sci. 2023 Apr 19;8(7):820-839. doi: 10.1016/j.jacbts.2022.12.013. eCollection 2023 Jul.
B-cell lymphoma 2-associated athanogene-3 (Bag3) is expressed in all animal species, with Bag3 levels being most prominent in the heart, the skeletal muscle, the central nervous system, and in many cancers. Preclinical studies of Bag3 biology have focused on animals that have developed compromised cardiac function; however, the present studies were performed to identify the pathways perturbed in the heart even before the occurrence of clinical signs of dilatation and failure of the heart. These studies show that hearts carrying variants that knockout one allele of have significant alterations in multiple cellular pathways including apoptosis, autophagy, mitochondrial homeostasis, and the inflammasome.
B细胞淋巴瘤2相关抗生存基因3（Bag3）在所有动物物种中均有表达，其中Bag3水平在心脏、骨骼肌、中枢神经系统以及许多癌症中最为显著。Bag3生物学的临床前研究主要集中在心脏功能受损的动物身上；然而，目前的研究旨在确定在心脏出现扩张和衰竭的临床症状之前，心脏中哪些信号通路受到了干扰。这些研究表明，携带敲除一个等位基因变体的心脏在包括细胞凋亡、自噬、线粒体稳态和炎性小体在内的多个细胞信号通路中存在显著改变。
