PUBLICATION
Early-Life Stress Regulates Cardiac Development through an IL-4-Glucocorticoid Signaling Balance
- Authors
- Apaydin, D.C., Jaramillo, P.A.M., Corradi, L., Cosco, F., Rathjen, F.G., Kammertoens, T., Filosa, A., Sawamiphak, S.
- ID
- ZDB-PUB-201120-160
- Date
- 2020
- Source
- Cell Reports 33: 108404 (Journal)
- Registered Authors
- Corradi, Laura, Filosa, Alessandro, Sawamiphak, Suphansa
- Keywords
- Stat3, cardiomyocyte, cytokine, glucocorticoid, heart development, interleukin-4, stress, zebrafish
- MeSH Terms
-
- Adverse Childhood Experiences
- Animals
- Female
- Glucocorticoids/metabolism
- Interleukin-4/immunology
- Interleukin-4/metabolism*
- Interleukin-4/physiology
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mitosis
- Myocardium/metabolism
- Myocardium/pathology
- Myocytes, Cardiac/metabolism*
- Myocytes, Cardiac/physiology
- Receptors, Glucocorticoid/immunology
- Receptors, Glucocorticoid/metabolism*
- STAT3 Transcription Factor/metabolism
- Signal Transduction/physiology
- Zebrafish/metabolism
- Zebrafish Proteins/metabolism
- PubMed
- 33207196 Full text @ Cell Rep.
Citation
Apaydin, D.C., Jaramillo, P.A.M., Corradi, L., Cosco, F., Rathjen, F.G., Kammertoens, T., Filosa, A., Sawamiphak, S. (2020) Early-Life Stress Regulates Cardiac Development through an IL-4-Glucocorticoid Signaling Balance. Cell Reports. 33:108404.
Abstract
Stressful experiences early in life can increase the risk of cardiovascular diseases. However, it remains largely unknown how stress influences susceptibility to the disease onset. Here, we show that exposure to brain-processed stress disrupts myocardial growth by reducing cardiomyocyte mitotic activity. Activation of the glucocorticoid receptor (GR), the primary stress response pathway, reduces cardiomyocyte numbers, disrupts trabecular formation, and leads to contractile dysfunction of the developing myocardium. However, a physiological level of GR signaling is required to prevent cardiomyocyte hyperproliferation. Mechanistically, we identify an antagonistic interaction between the GR and the cytokine interleukin-4 (IL-4) as a key player in cardiac development. IL-4 signals transcription of key regulators of cell-cycle progression in cardiomyocytes via signal transducer and activator of transcription 3 (Stat3). GR, on the contrary, inhibits this signaling system. Thus, our findings uncover an interplay between stress and immune signaling pathways critical to orchestrating physiological growth of the heart.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping