Related Experiment Video
Updated: Jan 4, 2026
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
Hippo signaling does it again: arbitrating cardiac fibroblast identity and activation
Anne Katrine Z Johansen1, Jeffery D Molkentin1,2
1Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA.
Insights
The Hippo pathway regulates cardiac fibroblasts, maintaining them in a resting state. Its inactivation during disease stress triggers a switch to myofibroblasts, causing fibrosis and heart remodeling.
Area of Science:
- Cardiovascular Biology
- Cell Signaling
- Developmental Biology
Background:
- The Hippo pathway is crucial for tissue development and homeostasis.
- Cardiac fibroblasts are key players in heart disease and repair.
- Hippo signaling's role in adult cardiac fibroblasts was previously unclear.
Purpose of the Study:
- To investigate the role of Hippo signaling in cardiac fibroblast function.
- To determine how Hippo pathway inactivation affects cardiac fibroblasts during disease stress.
- To elucidate the mechanisms underlying fibroblast-mediated cardiac remodeling.
Main Methods:
- Utilized mouse models and cell culture systems.
- Analyzed gene expression and protein activity related to Hippo signaling and fibroblast phenotypes.
- Investigated cytokine signaling and immune cell activation.
Main Results:
- Hippo signaling maintains cardiac fibroblasts in a quiescent state.
- Inactivation of Hippo signaling induces fibroblast transition to a myofibroblast phenotype.
- This transition is linked to fibrosis and ventricular remodeling.
- Associated with increased cytokine signaling and myeloid cell activation.
Conclusions:
- Hippo pathway signaling is a critical regulator of cardiac fibroblast identity and function.
- Dysregulation of Hippo signaling in fibroblasts contributes to cardiac fibrosis and disease.
- Targeting Hippo signaling may offer therapeutic strategies for heart disease.
Abstract:
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 Genes and Development, 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.
Related Concept Videos
02:33Hedgehog Signaling Pathway
01:24Regulation of Angiogenesis and Blood Supply
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:09Introduction to Fibroblasts
01:22PI3K/mTOR/AKT Signaling Pathway