Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA.
Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Genes Dev. 2019 Nov 1;33(21-22):1457-1459. doi: 10.1101/gad.332791.119.
The Hippo pathway is an evolutionarily conserved kinase cascade that is fundamental for tissue development, homeostasis, and regeneration. In the developing mammalian heart, Hippo signaling regulates cardiomyocyte numbers and organ size. While cardiomyocytes in the adult heart are largely postmitotic, Hippo deficiency can increase proliferation of these cells and affect cardiac regenerative capacity. Recent studies have also shown that resident cardiac fibroblasts play a critical role in disease responsiveness and healing, and in this issue of , Xiao and colleagues (pp. 1491-1505) demonstrate that Hippo signaling also integrates the activity of fibroblasts in the heart. They show that Hippo signaling normally maintains the cardiac fibroblast in a resting state and, conversely, its inactivation during disease-related stress results in a spontaneous transition toward a myofibroblast state that underlies fibrosis and ventricular remodeling. This phenotypic switch is associated with increased cytokine signaling that promotes nonautonomous resident fibroblast and myeloid cell activation.
Hippo 通路是进化上保守的激酶级联反应，对组织发育、稳态和再生至关重要。在发育中的哺乳动物心脏中，Hippo 信号调节心肌细胞数量和器官大小。虽然成年心脏中的心肌细胞基本上是有丝分裂后的，但 Hippo 缺陷会增加这些细胞的增殖，并影响心脏的再生能力。最近的研究还表明，驻留的心脏成纤维细胞在疾病反应和愈合中起着关键作用，在本期的 中，Xiao 和同事（第 1491-1505 页）表明 Hippo 信号也整合了心脏中成纤维细胞的活性。他们表明 Hippo 信号通常使心脏成纤维细胞处于静止状态，相反，在与疾病相关的应激过程中其失活会导致自发向肌成纤维细胞状态的转变，从而导致纤维化和心室重构。这种表型转换与增加的细胞因子信号有关，该信号促进非自主的驻留成纤维细胞和髓样细胞的激活。
