Research Paper Volume 12, Issue 14 pp 15134—15156
Signatures of cell stress and altered bioenergetics in skin fibroblasts from patients with multiple sclerosis
- 1 Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
- 2 Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
- 3 Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN 55905, USA
Received: April 1, 2020 Accepted: June 5, 2020 Published: July 8, 2020https://doi.org/10.18632/aging.103612
How to Cite
Copyright © 2020 Wilkins et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Multiple sclerosis (MS) is a central nervous system inflammatory demyelinating disease and the most common cause of non-traumatic disability in young adults. Despite progress in the treatment of the active relapsing disease, therapeutic options targeting irreversible progressive decline remain limited. Studies using skin fibroblasts derived from patients with neurodegenerative disorders demonstrate that cell stress pathways and bioenergetics are altered when compared to healthy individuals. However, findings in MS skin fibroblasts are limited. Here, we collected skin fibroblasts from 24 healthy control individuals, 30 patients with MS, and ten with amyotrophic lateral sclerosis (ALS) to investigate altered cell stress profiles. We observed endoplasmic reticulum swelling in MS skin fibroblasts, and increased gene expression of cell stress markers including BIP, ATF4, CHOP, GRP94, P53, and P21. When challenged against hydrogen peroxide, MS skin fibroblasts had reduced resiliency compared to ALS and controls. Mitochondrial and glycolytic functions were perturbed in MS skin fibroblasts while exhibiting a significant increase in lactate production over ALS and controls. Our results suggest that MS skin fibroblasts have an underlying stress phenotype, which may be disease specific. Interrogating MS skin fibroblasts may provide patient specific molecular insights and aid in prognosis, diagnosis, and therapeutic testing enhancing individualized medicine.