To study the associations between SHP-1 methylation in normal epithelial tissues and demethylation in psoriasis

Abstract

SHP-1 promotor hypermethylation has been studied in hematopoietic cells and observed only in various types of lymphoma and leukemia. This study reports a contrasting situation in normal epithelial tissues and an association with skin pathogenesis, particularly in psoriasis. We investigated several cell lines, 5 epithelial and 6 hematopoietic cell lines. White blood cells from normal healthy donors and normal micro-dissected epithelium of kidney, liver, breast, cervix, lung, prostate, bladder and skin were also included. Interestingly, promoter 2 hypermethylation was apparent in all epithelial cell lines and tissues. However, distinctive degrees of demethlation were noted in some skin samples. The methylation patterns of each cell line corresponded to their mRNA isoforms, in that isoform I and II could not be detected with either promoter 1 or 2 hypermethylation, respectively. We further explored whether an enhanced degree of demethlation could be observed in various dermatopathology lesions from Psoriasis, squamous cell cancers (SCC) and eczema. Thrity seven skin lesion samples were detected SHP-1 methylation of promoter 1 and 2 by using COBRA and MSP technique, respectively. While the promoter 2 methylation levels of SCC, eczemas and normal skins were not different, a significant degree of demethylation can be observed in psoriatic skin lesions, (p<0.005). In addition, psoriatic skin displays a higher level of SHP-1 isoform II than normal skin (p<0.05). In conclusion, this study discovered an unprecedented role of SHP-1 methylation in tissue specific expression and its alteration in a non-malignant human disease besides the transcription inhibition in leukemia an lymphoma. Furthermore, the promoter demethylation may play an important role in skin pathogenesis by enhancing SHP-1 isoform II transcription in psoriatic skin lesions.