대한신장학회

논문분류	춘계학술대회 초록집
제목	The role of suppression of tumorigenicity-2 (ST2) in the peritoneal fibrosis and peritoneal dialysis (PD) outcomes
저자	Yong Chul Kim1, Ran-hui Cha4, Seung Hee Yang2, Sunhwa Lee1, Mi-yeon Yu1, Jae WooK Lee5, Kook-Hwan Oh1, Suhnggown Kim2, Yon Su Kim3
출판정보	2018; 2018(1):
키워드	soluble ST2 \| peritoneal dialysis \| peritoneal fibrosis
초록	Objectives: Peritoneal fibrosis (PF) is an intractable complication which leads to peritoneal membrane failure in peritoneal dialysis (PD). The aim of this study was to investigate the role of ST2 involved in PF. Methods: Samples of dialysate and clinical data were prospectively collected from 54 patients at Seoul National University Hospital between 2010 and 2016. Dialysate soluble ST2 (sST2) levels were measured after 1 month of PD initiation (baseline) using the ELISA technique. Immunohistochemistry stain of ST2 was performed in peritoneum tissue samples of chlorhexidine gluconate (CG)-induced PF mice and control. And fibrosis induced by TGF-β in primary cultured human mesothelial cells were evaluated with protein expressions. Anti-ST2 antibody was treated to explore the neutralizing effect of ST2 on PF. Results: Baseline dialysate sST2 (sST2-b) levels were 2063.4 ± 2457.8 pg/mL and mean duration of follow-up periods was 53.4 ± 18.8 months. We observed that patients who changed dialysis modality to hemodialysis due to PD failure had high sST2-b levels in peritoneal effluent compared with others (1576.2 ± 199.9 versus 4143.1 ± 1107.3, P = 0.03). High sST2-b was associated with a hazard ratio for PD failure of 7.72 (95% CI 1.10-54.3, P = 0.04) in a fully adjusted model. sST2-b showed a good performance of predicting PD failure; the area under the ROC curve was 0.784 (P = 0.001). ST2 was found in fibroblasts and mesothelial cells within the underlying submesothelial zones of CG-induced PF mice. We found that in primary culture mesothelial cells, TGF-β treatment increased protein expressions of ST2, fibronectin, snail and decreased expression of E-cadherin in a dose-dependent manner. Protein expressions of ST2 and fibronectin were decreased after anti-ST2 Ab administration. Conclusions: Elevated dialysate levels of ST2 appears to play a role in fibrosis and inflammation during peritoneal injury. Thus, ST2 blockade is a potential therapeutic target for renal preservation.
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