Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
Por:
Wagstaff LJ, Gomez-Sanchez JA, Fazal SV, Otto GW, Kilpatrick AM, Michael K, Wong LYN, Ma KH, Turmaine M, Svaren J, Gordon T, Arthur-Farraj P, Velasco-Aviles S, Cabedo H, Benito C, Mirsky R and Jessen KR
Publicada:
21 ene 2021
Ahead of Print:
21 ene 2021
Resumen:
After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems. In mice, we find that repair cells express reduced c-Jun protein as regenerative support provided by these cells declines during aging and chronic denervation. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to control levels. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. This establishes that a common mechanism, reduced c-Jun in Schwann cells, regulates success and failure of nerve repair both during aging and chronic denervation. This provides a molecular framework for addressing important clinical problems, suggesting molecular pathways that can be targeted to promote repair in the PNS.
Filiaciones:
Wagstaff LJ:
Department of Cell and Developmental Biology, University College London, London, United Kingdom
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
Fazal SV:
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Otto GW:
University College London Great Ormond Street Institute of Child Health, London, United Kingdom
Kilpatrick AM:
Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom
Michael K:
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Wong LYN:
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Ma KH:
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, United States
Turmaine M:
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Svaren J:
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, United States
Gordon T:
Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, Canada
Arthur-Farraj P:
John Van Geest Centre for Brain repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
Hospital General Universitario de Alicante, ISABIAL, Alicante, Spain
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
Hospital General Universitario de Alicante, ISABIAL, Alicante, Spain
Benito C:
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Mirsky R:
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Jessen KR:
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Gold, Green Published
|