NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies.
Animals
Animals, Genetically Modified
Charcot-Marie-Tooth Disease
/ genetics
Demyelinating Diseases
/ genetics
Diabetes Mellitus, Type 1
/ complications
Diabetic Neuropathies
/ etiology
Humans
MAP Kinase Signaling System
Mice
Mice, Transgenic
Microscopy, Electron
Motor Activity
Myelin Proteins
/ genetics
Neuregulin-1
/ genetics
Neuritis, Autoimmune, Experimental
/ genetics
Neuroglia
/ metabolism
Paracrine Communication
Rats
Receptor, ErbB-2
/ metabolism
Schwann Cells
/ metabolism
Sciatic Nerve
/ injuries
Signal Transduction
Sural Nerve
/ metabolism
Tibial Nerve
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 04 2019
01 04 2019
Historique:
received:
29
12
2018
accepted:
07
03
2019
entrez:
2
4
2019
pubmed:
2
4
2019
medline:
17
4
2019
Statut:
epublish
Résumé
In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases. Genetic disruption of Schwann cell-derived NRG1 signalling in a mouse model of Charcot-Marie-Tooth Disease 1A (CMT1A), suppresses hypermyelination and the formation of onion bulbs. Transgenic overexpression of NRG1-I in Schwann cells on a wildtype background is sufficient to mediate an interaction between Schwann cells via an ErbB2 receptor-MEK/ERK signaling axis, which causes onion bulb formations and results in a peripheral neuropathy reminiscent of CMT1A. We suggest that diseased Schwann cells mount a regeneration program that is beneficial in acute nerve injury, but that overstimulation of Schwann cells in chronic neuropathies is detrimental.
Identifiants
pubmed: 30931926
doi: 10.1038/s41467-019-09385-6
pii: 10.1038/s41467-019-09385-6
pmc: PMC6443727
doi:
Substances chimiques
Myelin Proteins
0
NRG1 protein, human
0
Neuregulin-1
0
Nrg1 protein, mouse
0
Nrg1 protein, rat
0
PMP22 protein, human
0
Erbb2 protein, mouse
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1467Commentaires et corrections
Type : ErratumIn
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