Related Experiment Video
Updated: Jan 28, 2026
06:54
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
14.3K
Cardiomyocyte SMAD4-Dependent TGF-β Signaling is Essential to Maintain Adult Heart Homeostasis
Prachi Umbarkar1, Anand P Singh1, Manisha Gupte1
1Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
JACC. Basic to Translational Science
|March 9, 2019
Summary
Transforming growth factor-beta (TGF-β) signaling mediated by SMAD4 in cardiomyocytes is vital for heart function and survival. Inhibiting TGF-β systemically may harm cardiac health, despite its role in fibrosis.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cell Signaling
Background:
- The transforming growth factor-beta (TGF-β) pathway is implicated in myocardial fibrosis.
- The specific role of TGF-β signaling within cardiomyocytes (CMs) remains unclear.
- SMAD4 is a key intracellular mediator in TGF-β signaling.
Purpose of the Study:
- To elucidate the function of TGF-β signaling in adult cardiomyocyte biology.
- To investigate the necessity of SMAD4 in CMs for cardiac homeostasis.
Main Methods:
- Deletion of SMAD4 specifically in adult mouse cardiomyocytes.
- Assessment of cardiac function, sarcomere kinetics, and gene expression.
Main Results:
- CM-SMAD4-dependent TGF-β signaling is essential for maintaining cardiac function.
- This pathway regulates sarcomere kinetics and ion-channel gene expression.
- SMAD4 in CMs is critical for cardiomyocyte survival.
Conclusions:
- TGF-β signaling via SMAD4 in cardiomyocytes is crucial for normal cardiac physiology.
- Systemic inhibition of TGF-β for fibrosis treatment warrants caution due to potential adverse effects on CMs.
Keywords:
CM, cardiomyocyteCSA, cross-sectional areaCTL, controlDCM, dilated cardiomyopathyKO, knockoutLV, left ventricle/ventricularMAPK, mitogen-activated protein kinaseMCM, MerCreMerPI3K, phosphoinositide-3 kinaseRNA-Seq, RNA sequencingSMAD4TAK1, transforming growth factor beta–activated kinase 1TAM, tamoxifenTGF, transforming growth factorTGF-βcMyBP-C, cardiac myosin-binding protein Ccardiomyocytecardiomyopathyfibrosisheart failure
Related Concept Videos
01:16TGF - β Signaling Pathway
10.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.5K
01:19Contact-dependent Signaling
46.9K
Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
Gap Junctions
In animal cells, gap junctions are formed...
46.9K
01:16Calmodulin-dependent Signaling
6.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
6.1K
02:26NF-κB-dependent Signaling Pathway
10.0K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.0K
01:16What is Homeostasis?
53.7K
Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, from body temperature to blood pressure to levels of certain nutrients. A set point is the physiological value around which the normal range fluctuates. A normal range is a restricted set of values that is optimally healthful and stable. For example, the set point for normal human body temperature is approximately 37°C (98.6°F).
53.7K
01:22Heart Failure Drugs: β-Blockers
886
β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...
886