Gene expression profiling in nerve biopsy of vasculitic neuropathy.
To investigate molecular mechanisms of peripheral nerve vasculitis, gene expression patterns in archived frozen sural nerve biopsies from patients with vasculitic neuropathy were compared to control nerves by DNA microarray technology. There was a striking upregulation of mRNA of genes involved in immune system processes. Of special interest was the activation of immunoglobulin genes, such as IGLJ3, IGHG3, IGKC, and IGL, and of several chemokines, such as CXCL9 or CCR2. Genes involved in vascular proliferation or remodelling such as CXC31 and AIF were also upregulated. Among the downregulated genes were the Krüppel-Like Transcription Factors KLF2, KLF4 and the nuclear orphan receptor NR4A1 genes known to be involved in endothelial cell activation. Thus, this gene expression profile analysis revealed that in peripheral nerve vasculitis a prominent activation of immune response related genes as well as genes involved in vascular proliferation is taken place, while genes inhibiting endothelial cell activation are down regulated. These data point to interesting mechanistic clues to the molecular pathogenesis of vasculitic neuropathies.
Kinter
Jochen
J
Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Broglio
Laura
L
Steck
Andreas J
AJ
Tolnay
Markus
M
Fuhr
Peter
P
Latov
Norman
N
Kalbermatten
Daniel
D
Sinnreich
Michael
M
Schaeren-Wiemers
Nicole
N
Renaud
Susanne
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy / Q000379:methods; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013497:Sural Nerve / Q000276:immunology / Q000378:metabolism*; D014657:Vasculitis / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1