Upregulation of c-Myc may contribute to the pathogenesis of canine pemphigus vulgaris.
The pathomechanism in human pemphigus vulgaris (PV) has recently been described to rely on generalized c-Myc upregulation in skin and oral mucosa followed by hyperproliferation. Here we assessed whether dogs suffering from PV present the same pathological changes as described for human patients with PV. Using immunofluorescence analysis on patients' biopsy samples, we observed marked nuclear c-Myc accumulation in all layers of the epidermis and oral mucosa in all (3/3) dogs analysed. In addition, c-Myc upregulation was accompanied by an increased number of proliferating Ki67-positive cells. These molecular changes were further paralleled by deregulated expression of wound healing and terminal differentiation markers as observed in human PV. Together these findings suggest a common pathomechanism for both species which is of particular relevance in the light of the recently discussed novel therapeutic strategies aiming at targeting PV antibody-induced signalling cascades.
Williamson
Lina
L
Molecular Dermatology, Institute Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Suter
Maja M
MM
Olivry
Thierry
T
Wyder
Marianne
M
Müller
Eliane J
EJ
D000818:Animals; D016022:Case-Control Studies; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005455:Fluorescent Antibody Technique / Q000662:veterinary; D006801:Humans; D009061:Mouth Mucosa / Q000378:metabolism; D010392:Pemphigus / Q000378:metabolism / Q000662:veterinary*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D015854:Up-Regulation
D016271:Proto-Oncogene Proteins c-myc