Sartori Roberta, Sandri Marco
aDulbecco Telethon Institute, Venetian Institute of Molecular Medicine bDepartment of Biomedical Sciences, University of Padova, Padova cTelethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy.
Curr Opin Clin Nutr Metab Care. 2015 May;18(3):215-20. doi: 10.1097/MCO.0000000000000172.
The purpose of this study is to discuss the involvement of bone and morphogenetic proteins (BMPs) in the control of muscle mass.
The transforming growth factor-beta (TGFβ) superfamily comprises a large number of secreted proteins that regulate a variety of fundamental biological processes. Sequence similarities define two ligand subfamilies: the TGFβ/Activin subfamily and the BMP subfamily. Within the members of TGFβ subfamily, myostatin emerged as the most critical ligand that affects muscle size and function. Indeed, mutations that inactivate Myostatin lead to important muscle growth in animals and humans. However, recent findings have increased the complexity of the TGFβ superfamily. Indeed, two independent groups have shown that BMP pathway, acting through Smad1/5/8, is the fundamental hypertrophic signal and dominates Myostatin signalling. Moreover, BMP-Smad1/5/8 negatively regulates a novel ubiquitin ligase, named MUSA1 that is required for muscle loss. This article reviews the rapid progress made in the last year regarding the signalling downstream TGFβ superfamily and its involvement in the homeostasis of adult muscle fibres.
The recent insights gained into the interplay of TGFβ and BMP signalling in muscle have challenged our pre-existing ideas of how the adult skeletal muscle phenotype is regulated in health and disease.
本研究旨在探讨骨形态发生蛋白（BMPs）在肌肉量控制中的作用。
转化生长因子-β（TGFβ）超家族由大量分泌蛋白组成，这些蛋白调节多种基本生物学过程。序列相似性定义了两个配体亚家族：TGFβ/激活素亚家族和BMP亚家族。在TGFβ亚家族成员中，肌肉生长抑制素是影响肌肉大小和功能的最关键配体。事实上，使肌肉生长抑制素失活的突变会导致动物和人类肌肉显著生长。然而，最近的发现增加了TGFβ超家族的复杂性。的确，两个独立的研究小组表明，通过Smad1/5/8起作用的BMP信号通路是基本的肥大信号，并且主导肌肉生长抑制素信号通路。此外，BMP-Smad1/5/8负向调节一种新的泛素连接酶，名为MUSA1，它是肌肉损失所必需的。本文综述了去年在TGFβ超家族下游信号及其在成年肌纤维稳态中的作用方面取得的快速进展。
最近对肌肉中TGFβ和BMP信号相互作用的深入了解挑战了我们之前关于健康和疾病状态下成年骨骼肌表型如何调节的观念。
