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논문분류	춘계학술대회 초록집
제목	Uremic solutes of indoxyl sulfate and p-cresol enhance proteaseactivated receptor-2 expression in human skin and a chronic kidney disease mouse model
저자	*Sung jin MOON2, Seung jun KIM2, Chan ho KIM2, Mirae LEE3, Zhenlong ZHENG4, Sung bin CHO4, Hyeong-cheon PARK3
출판정보	2017; 2017(1):
키워드	Chronic kidney disease, uremic solute, protease activated receptor-2, indoxyl sulfate, p-cresol
초록	Objectives : Protein-bound uremic solutes are not effectively eliminated by dialysis, and and hold biochemical significance in patients with chronic kidney disease (CKD). Recently, activation of protease-activated receptor-2 (PAR-2) has been suggested to play an important role in uremic pruritus. The aim of this study was to investigate the effects of uremic solutes on the expression of PAR-2 in human skin and a CKD mouse model. Methods : Indoxyl sulfate (IS), p-cresol (PC), and uremic sera from CKD patients were used to stimulate PAR-2 expression in normal human epidermal keratinocytes (NHEKs). NHEKs were additionally pretreated with soybean trypsin inhibitor to evaluate its inhibitory effect on PAR-2 expression. Patterns of cutaneous PAR-2 expression were investigated in skin samples from five CKD patients with uremic pruritus and the CKD mice. Results : In both dose-dependent and time-dependent manner, IS and PC increased PAR-2 expression in NHEKs at mRNA and protein levels. NHEKs treated with uremic sera also exhibited significant increases in PAR-2 mRNA and protein expression. Immunohistochemical staining of skin samples from CKD patients and CKD mice revealed marked increases in cutaneous PAR-2 expression in the cytoplasm of epidermal cells, compared to that in skin samples from healthy human and mouse controls. The noted increases in PAR- 2 mRNA and protein expression were significantly inhibited by pretreatment with soybean trypsin inhibitor. Conclusions : The present study suggests that uremic solutes, especially IS and PC, induce PAR-2 expression in NHEKs, and these molecules could play an important function in the pathogenesis of uremic pruritus in CKD patients.
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