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Journal of Cellular and Molecular Medicine, 2019. 10, 6872-6884, DOI: https://doi.org/10.1111/jcmm.14571
ST2 blockade mitigates peritoneal fibrosis induced by TGF-β and high glucose
Yong Chul Kim, Kyu Hong Kim;Sunhwa Lee;Ji‐won Jo;Jae Yoon Park;Mi‐seon Park;Bodokhsuren Tsogbadrakh;Jung Pyo Lee;Jae Wook Lee;Dong Ki Kim;Kook‐Hwan Oh;In‐Jin Jang;Yon Su Kim;Ran‐hui Cha;Seung Hee Yang
Peritoneal fibrosis (PF) is an intractable complication of peritoneal dialysis (PD) that leads to peritoneal membrane failure. This study investigated the role of suppression of tumorigenicity (ST)2 in PF using patient samples along with mouse and cell‐based models. Baseline dialysate soluble (s)ST2 level in patients measured 1 month after PD initiation was 2063.4 ± 2457.8 pg/mL; patients who switched to haemodialysishad elevated sST2 levels in peritoneal effluent (1576.2 ± 199.9 pg/mL, P = .03), whichwas associated with PD failure (P = .04). Baseline sST2 showed good performance inpredicting PD failure (area under the receiver operating characteristic curve = 0.780, P = .001). In mice with chlorhexidine gluconate‐induced PF, ST2 was expressed infibroblasts and mesothelial cells within submesothelial zones. In primary culturedhuman peritoneal mesothelial cells (HPMCs), transforming growth factor‐β treatment increased ST2, fibronectin, β‐galactosidase and Snail protein levels and decreased E‐cadherin level. Anti‐ST2 antibody administration reversed the up‐regulation of ST2 and fibronectin expression; it also reduced fibrosis induced by high glucose(100 mmol/L) in HPMCs. Thus, high ST2 level in dialysate is a marker for fibrosis and inflammation during peritoneal injury, and blocking ST2 may be an effective therapeutic strategy for renal preservation.
- DOI: https://doi.org/10.1111/jcmm.14571
- ISBN or ISSN: 1582-1838
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.