Nature Communications (Jan 2019)
The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis
- Hannah V. Woodcock,
- Jessica D. Eley,
- Delphine Guillotin,
- Manuela Platé,
- Carmel B. Nanthakumar,
- Matteo Martufi,
- Simon Peace,
- Gerard Joberty,
- Daniel Poeckel,
- Robert B. Good,
- Adam R. Taylor,
- Nico Zinn,
- Matthew Redding,
- Ellen J. Forty,
- Robert E. Hynds,
- Charles Swanton,
- Morten Karsdal,
- Toby M. Maher,
- Andrew Fisher,
- Giovanna Bergamini,
- Richard P. Marshall,
- Andy D. Blanchard,
- Paul F. Mercer,
- Rachel C. Chambers
Affiliations
- Hannah V. Woodcock
- Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London
- Jessica D. Eley
- Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London
- Delphine Guillotin
- Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London
- Manuela Platé
- Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London
- Carmel B. Nanthakumar
- Fibrosis Discovery Performance Unit, Respiratory Therapy Area, Medicines Research Centre, GlaxoSmithKline R&D
- Matteo Martufi
- Target Sciences, Medicines Research Centre, GlaxoSmithKline R&D
- Simon Peace
- Fibrosis Discovery Performance Unit, Respiratory Therapy Area, Medicines Research Centre, GlaxoSmithKline R&D
- Gerard Joberty
- Cellzome, a GSK Company
- Daniel Poeckel
- Cellzome, a GSK Company
- Robert B. Good
- Fibrosis Discovery Performance Unit, Respiratory Therapy Area, Medicines Research Centre, GlaxoSmithKline R&D
- Adam R. Taylor
- Fibrosis Discovery Performance Unit, Respiratory Therapy Area, Medicines Research Centre, GlaxoSmithKline R&D
- Nico Zinn
- Cellzome, a GSK Company
- Matthew Redding
- Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London
- Ellen J. Forty
- Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London
- Robert E. Hynds
- CRUK Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London
- Charles Swanton
- CRUK Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London
- Morten Karsdal
- Nordic Bioscience
- Toby M. Maher
- Fibrosis Research Group, Inflammation, Repair & Development Section, NHLI, Imperial College
- Andrew Fisher
- Newcastle Fibrosis Research Group, Newcastle University Translational and Clinical Research Institute
- Giovanna Bergamini
- Cellzome, a GSK Company
- Richard P. Marshall
- Fibrosis Discovery Performance Unit, Respiratory Therapy Area, Medicines Research Centre, GlaxoSmithKline R&D
- Andy D. Blanchard
- Fibrosis Discovery Performance Unit, Respiratory Therapy Area, Medicines Research Centre, GlaxoSmithKline R&D
- Paul F. Mercer
- Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London
- Rachel C. Chambers
- Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London
- DOI
- https://doi.org/10.1038/s41467-018-07858-8
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 16
Abstract
The PI3K/Akt/mTOR pathway has been previously implicated in fibrosis and a pan-PI3K/mTOR inhibitor is currently under clinical evaluation for the treatment of IPF. Here the authors show that the mTORC1/4E-BP1 axis is critical for TGF-β1-induced fibrogenesis in in vitro and ex vivo models and that canonical PI3K/Akt signalling is dispensable.
