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Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis

Authors
 Bo Young Nam  ;  Jung Tak Park  ;  Young Eun Kwon  ;  Jung Pyo Lee  ;  Jong Ha Jung  ;  Youndong Kim  ;  Seonghun Kim  ;  Jimin Park  ;  Jae Eun Um  ;  Meiyan Wu  ;  Seung Hyeok Han  ;  Tae-Hyun Yoo  ;  Shin-Wook Kang 
Citation
 Molecular Therapy. Nucleic Acids, Vol.7 : 396-407, 2017 
Journal Title
 Molecular Therapy. Nucleic Acids 
Issue Date
2017
Keywords
TGF-β1 ; aptamer ; fibrosis ; periostin ; peritoneal dialysis
Abstract
Peritoneal fibrosis is a major complication in peritoneal dialysis (PD) patients, which leads to dialysis discontinuation. Periostin, increased by transforming growth factor β1 (TGF-β1) stimulation, induces the expression of extracellular matrix (ECM) genes. Aberrant periostin expression has been demonstrated to be associated with PD-related peritoneal fibrosis. Therefore, the effect of periostin inhibition by an aptamer-based inhibitor on peritoneal fibrosis was evaluated. In vitro, TGF-β1 treatment upregulated periostin, fibronectin, α-smooth muscle actin (α-SMA), and Snail expression and reduced E-cadherin expression in human peritoneal mesothelial cells (HPMCs). Periostin small interfering RNA (siRNA) treatment ameliorated the TGF-β1-induced periostin, fibronectin, α-SMA, and Snail expression and restored E-cadherin expression in HPMCs. Similarly, the periostin-binding DNA aptamer (PA) also attenuated fibronectin, α-SMA, and Snail upregulation and E-cadherin downregulation in TGF-β1-stimulated HPMCs. In mice treated with PD solution for 4 weeks, the expression of periostin, fibronectin, α-SMA, and Snail was significantly increased in the peritoneum, whereas E-cadherin expression was significantly decreased. The thickness of the submesothelial layer and the intensity of Masson's trichrome staining in the PD group were significantly increased compared to the untreated group. These changes were significantly abrogated by the intraperitoneal administration of PA. These findings suggest that PA can be a potential therapeutic strategy for peritoneal fibrosis in PD patients.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/160241
DOI
10.1016/j.omtn.2017.05.001
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
강신욱(Kang, Shin Wook) ; 권영은(Kwon, Young Eun) ; 박정탁(Park, Jung Tak) ; 유태현(Yoo, Tae Hyun) ; 한승혁(Han, Seung Hyeok)
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