Open AccessST2 blockade mitigates peritoneal fibrosis induced by TGF‐β and high glucose
Author(s) -
Kim Yong Chul,
Kim Kyu Hong,
Lee Sunhwa,
Jo Jiwon,
Park Jae Yoon,
Park Miseon,
Tsogbadrakh Bodokhsuren,
Lee Jung Pyo,
Lee Jae Wook,
Kim Dong Ki,
Oh KookHwan,
Jang InJin,
Kim Yon Su,
Cha Ranhui,
Yang Seung Hee
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14571
Subject(s) - peritoneal dialysis , fibrosis , medicine , fibronectin , transforming growth factor , inflammation , blockade , peritoneum , mesothelial cell , receptor , downregulation and upregulation , urology , endocrinology , pathology , cell , chemistry , biochemistry , gene
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 haemodialysis had elevated sST2 levels in peritoneal effluent (1576.2 ± 199.9 pg/mL, P = .03), which was associated with PD failure ( P = .04). Baseline sST2 showed good performance in predicting PD failure (area under the receiver operating characteristic curve = 0.780, P = .001). In mice with chlorhexidine gluconate‐induced PF, ST2 was expressed in fibroblasts and mesothelial cells within submesothelial zones. In primary cultured human 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.