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Updated: Jun 20, 2026
Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
Published on: July 30, 2018
Bioluminescence analysis of Smad-dependent TGF-beta signaling in live mice
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Abstract:
TGF-beta signaling via the Smad2/3 pathway has key roles in development and tissue homeostasis. Perturbations of the TGF-beta signaling are involved in the pathogenesis of many human diseases, including cancer, fibrotic disorders, developmental defects, and neurodegeneration. To study the temporal and spatial patterns of Smad2/3-dependent signaling in living animals, we engineered transgenic mice with a Smad-responsive luciferase reporter (SBE-luc mice). Smad2/3-dependent signaling can be assessed non-invasively in living mice by bioluminescence imaging. To identify the cellular source of the bioluminescence signal, we generated new reporter mice expressing a trifusion protein containing luciferase, red fluorescent protein (RFP), and thymidine kinase under the control of the same SBE promoter (SBE-lucRT mice). SBE-luc and SBE-lucRT mice can be used to study temporal, tissue-specific activation of Smad2/3-dependent signaling in living mice as well as for the identification of endogenous or synthetic modulators of this pathway.
Insights
We developed novel transgenic mice to track TGF-beta Smad2/3 signaling non-invasively. These SBE-luc and SBE-lucRT mice enable real-time studies of signaling dynamics in living animals.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Transforming Growth Factor-beta (TGF-β) signaling through the Smad2/3 pathway is crucial for development and maintaining tissue health.
- Dysregulation of TGF-β signaling is implicated in various diseases, including cancer, fibrosis, developmental abnormalities, and neurodegenerative disorders.
Purpose of the Study:
- To develop innovative tools for non-invasively monitoring Smad2/3-dependent TGF-β signaling in vivo.
- To enable the study of temporal and spatial signaling patterns in living animals.
- To facilitate the identification of cellular sources of signaling and potential pathway modulators.
Main Methods:
- Engineering of transgenic mice (SBE-luc) harboring a Smad-responsive luciferase reporter.
- Utilizing bioluminescence imaging for non-invasive assessment of Smad2/3 signaling in live mice.
- Generation of SBE-lucRT mice expressing a trifusion protein (luciferase, RFP, thymidine kinase) for cellular signal localization.
Main Results:
- SBE-luc mice allow for non-invasive, real-time monitoring of Smad2/3 pathway activity via bioluminescence.
- SBE-lucRT mice enable precise identification of the cellular origins of the bioluminescence signal.
- These reporter systems provide a powerful platform for studying TGF-β signaling dynamics in vivo.
Conclusions:
- SBE-luc and SBE-lucRT mice are valuable tools for investigating Smad2/3-dependent TGF-β signaling in living organisms.
- These models facilitate research into the role of TGF-β signaling in health and disease.
- The reporter systems can be used to screen for novel modulators of the TGF-β pathway.
