Involvement of impaired desmosome-related proteins in hypertrophic scar intraepidermal blister formation

Abstract

Hypertrophic scar is one of the unique fibrotic diseases in human. Intraepidermal blister is a common clinical symptom following the hypertrophic scar formation. However, little is known about the reason of blister creation. In this study, we selected three patients with hypertrophic scar as manifested by raised, erythematous, pruritic, blister and thickened appearance undergoing scar resection. The first scar sample was 6 months after burn from the neck of a 3 years old male patient with 10 score by Vancouver Scar Scale (VSS). The second scar sample was 12 months after burn from the dorsal foot of a 16 years old female patient with 13 score by VSS. The third one was 9 months after burn from the elbow of a 34 years old male patients with 13 score by VSS. In order to understand the molecular mechanism of blister formation, we screened the different protein expression between hypertrophic scar and normal skin tissue by means of isobaric tags for relative and absolute quantitation (iTRAQ) labeling technology and high throughput 2D LC-MS/MS. There were 48 proteins found to be downregulated in hypertrophic scar. Among the downregulated ones, plakophilin1 (PKP1), plakophilin3 (PKP3) and desmoplakin (DSP) were the desmosome-related proteins which were validated by immunohistochemistry and western blotting assay. Transmission electron microscopy further showed the considerably reduced size and intensity of hemidesmosome and desmosome in hypertrophic scar tissue, compared to control normal skin. Our data indicted for the first time that downregulation of DSP, PKP1 and PKP3 in hypertrophic scar might be responsible for intraepidermal blister formation.