Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
J Exp Med. 2021 May 3;218(5). doi: 10.1084/jem.20201206.
Meteorin-like/Meteorin-β (Metrnl/Metrnβ) is a secreted protein produced by skeletal muscle and adipose tissue that exerts metabolic actions that improve glucose metabolism. The role of Metrnβ in cardiac disease is completely unknown. Here, we show that Metrnβ-null mice exhibit asymmetrical cardiac hypertrophy, fibrosis, and enhanced signs of cardiac dysfunction in response to isoproterenol-induced cardiac hypertrophy and aging. Conversely, adeno-associated virus-mediated specific overexpression of Metrnβ in the heart prevents the development of cardiac remodeling. Furthermore, Metrnβ inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrnβ in cardiomyocyte cell cultures indicated an autocrine action of Metrnβ on the heart, in addition to an endocrine action. Moreover, Metrnβ is highly produced in the heart, and analysis of circulating Metrnβ concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value.
类流星体蛋白/流星体-β（Metrnl/Metrnβ）是一种由骨骼肌和脂肪组织产生的分泌蛋白，具有改善葡萄糖代谢的代谢作用。Metrnβ 在心脏病中的作用尚完全不清楚。在这里，我们显示 Metrnβ 基因敲除小鼠表现出不对称性心肌肥厚、纤维化，并在异丙肾上腺素诱导的心肌肥厚和衰老时增强心脏功能障碍的迹象。相反，腺相关病毒介导的 Metrnβ 在心脏中的特异性过表达可预防心脏重构的发生。此外，Metrnβ 在体外抑制心肌细胞中的心肌肥厚发育，表明对心脏细胞有直接作用。在心肌细胞培养物中用抗体阻断 Metrnβ 表明 Metrnβ 在心内除内分泌作用之外还有自分泌作用。此外，Metrnβ 在心脏中大量产生，并且对一大群患者的循环 Metrnβ 浓度的分析表明它是心力衰竭的一个新的生物标志物，具有独立的预后价值。
