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Updated: Feb 7, 2026
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Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle
Published on: October 26, 2017
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Nrf2-Mediated Fibroblast Reprogramming Drives Cellular Senescence by Targeting the Matrisome
Paul Hiebert1, Mateusz S Wietecha1, Michael Cangkrama1
1Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology (ETH) Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland.
Developmental Cell
|July 18, 2018
Summary
Activating Nrf2 (Nuclear factor erythroid 2-related factor 2) in fibroblasts triggers cellular senescence and promotes wound healing, but also skin tumor development. This suggests Nrf2
Area of Science:
- Cellular biology
- Molecular mechanisms of aging and cancer
Background:
- Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of cellular antioxidant responses.
- Pharmacological activation of Nrf2 is explored for cancer prevention and tissue repair.
- However, the precise role of Nrf2 in fibroblast function and its dual effects remain incompletely understood.
Purpose of the Study:
- To investigate the effects of Nrf2 activation in fibroblasts on cellular senescence and matrix deposition.
- To determine the in vivo consequences of fibroblast Nrf2 activation on wound healing and tumorigenesis.
- To assess the relevance of Nrf2-induced fibroblast changes to cancer-associated fibroblast phenotypes.
Main Methods:
- Transcriptomics and matrix proteomics to analyze gene and protein expression.
- Chromatin immunoprecipitation to study Nrf2 binding.
- Bioinformatic analyses to interpret molecular data.
- In vivo studies using mouse models for wound healing and skin tumorigenesis.
Main Results:
- Fibroblast-specific Nrf2 activation induced cellular senescence and the deposition of a senescence-promoting extracellular matrix.
- Plasminogen activator inhibitor-1 was identified as a key mediator of Nrf2-induced senescence.
- In vivo, Nrf2 activation in fibroblasts enhanced skin wound re-epithelialization but also promoted skin tumorigenesis.
- Nrf2 activation in fibroblasts upregulated genes characteristic of cancer-associated fibroblasts in various tumors.
Conclusions:
- Fibroblast Nrf2 activation has a dual role, promoting both tissue repair and tumorigenesis.
- Activated Nrf2 is a potential marker for cancer-associated fibroblasts.
- Temporal control of Nrf2 activation is critical for therapeutic applications.
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