NRP-1 Receptor Expression Mismatch in Skin of Subjects with Experimental and Diabetic Small Fiber Neuropathy.
The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1)/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes.
Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.|HistoGeneX NV, Antwerp, Belgium.
Nathalie
N
Van Acker
Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.
Michael
M
Ragé
HistoGeneX NV, Antwerp, Belgium.
Hilde
H
Vermeirsch
HistoGeneX NV, Antwerp, Belgium.
Dorien
D
Schrijvers
Janssen Research and Development, Janssen Pharmaceutics NV, Beerse, Belgium.
Rony
R
Nuydens
Janssen Research and Development, Janssen Pharmaceutics NV, Beerse, Belgium.
Geert
G
Byttebier
Janssen Research and Development, Janssen Pharmaceutics NV, Beerse, Belgium.|Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Maarten
M
Timmers
HistoGeneX NV, Antwerp, Belgium.
Stefanie
S
De Schepper
Janssen Research and Development, Janssen Pharmaceutics NV, Beerse, Belgium.|Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Johannes
J
Streffer
HistoGeneX NV, Antwerp, Belgium.
Luc
L
Andries
Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.
Léon
L
Plaghki
Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.|Department of Neurology, Antwerp University Hospital, Born Bunge Institute, University of Antwerp, Antwerp, Belgium.
Patrick
P
Cras
Janssen Research and Development, Janssen Pharmaceutics NV, Beerse, Belgium.
Theo
T
Meert
D000328:Adult; D000368:Aged; D001706:Biopsy; D002211:Capsaicin / Q000378:metabolism; D048909:Diabetes Complications / Q000235:genetics* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000235:genetics* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics; D039942:Neuropilin-1 / Q000096:biosynthesis* / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D000071075:Small Fiber Neuropathy / Q000235:genetics* / Q000473:pathology
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D039942:Neuropilin-1; D002211:Capsaicin