Reduced gene expression of netrin family members in skin and sural nerve specimens of patients with painful peripheral neuropathies
To investigate the expression of axon guidance cues in skin and sural nerve biopsies of patients with polyneuropathies (PNP) as potential markers of nerve de- and regeneration and inflammation.
We prospectively recruited 88 patients with PNP and compared data between patient subgroups and healthy controls. All patients underwent skin punch and/or sural nerve biopsy at the lower leg and proximal thigh. We characterized gene expression profiles of netrin family members as target genes involved in neuronal de- and regeneration [netrin 1, deleted in colorectal cancer (DCC), uncoordinated5H2, neogenin 1 (NEO1), netrin G1, netrin G2] using quantitative real-time PCR.
Gene expression of netrin 1 (p < 0.05 in proximal skin), DCC (p < 0.001 in distal skin), NEO1 (p < 0.05 in distal skin), netrin G1 (p < 0.05 in proximal and p < 0.01 in distal skin), and netrin G2 (p < 0.001 in distal skin) was lower in skin biopsies of patients with neuropathy compared to healthy controls. Gene expression of NEO1 (p < 0.05 in distal skin), netrin G2 (p < 0.05 in distal skin), and DCC (p < 0.05 in sural nerve) was lower in samples of patients with painful compared to painless PNP and also correlated positively with intraepidermal nerve fiber density. Skin and sural nerve gene expression of the investigated target genes did not differ between neuropathies of different etiologies.
We show reduced cutaneous and neural axon guide expression, which may contribute to a dysregulation of nerve fiber de- and regeneration.
KeywordsPolyneuropathy Axon guides Netrin-1 Gene expression Skin biopsy Nerve biopsy
Our study was supported by intramural funds of the University of Würzburg. N.Ü. was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG; Grant no. UE171-5/1).
Compliance with ethical standards
Conflicts of interest
The authors declare no conflicts of interest.
Our study was approved by the Würzburg Medical Faculty Ethics Committee (85/06) and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
All participants gave written informed consent before study inclusion.
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