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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)396-407
Number of pages12
JournalMolecular Therapy - Nucleic Acids
Volume7
DOIs
Publication statusPublished - 2017 Jun 1

Fingerprint

Peritoneal Fibrosis
Nucleotide Aptamers
Peritoneal Dialysis
Transforming Growth Factors
Cadherins
Fibronectins
Snails
Therapeutics
Peritoneum
Dialysis Solutions
Small Interfering RNA
Extracellular Matrix
Smooth Muscle
Actins
Dialysis
Up-Regulation
Down-Regulation
Staining and Labeling
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Nam, Bo Young ; Park, Jung Tak ; Kwon, Young Eun ; Lee, Jung Pyo ; Jung, Jong Ha ; Kim, Youndong ; Kim, Seonghun ; Park, Jimin ; Um, Jae Eun ; Wu, Meiyan ; Han, Seung Hyeok ; Yoo, Tae Hyun ; Kang, Shin Wook. / Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis. In: Molecular Therapy - Nucleic Acids. 2017 ; Vol. 7. pp. 396-407.
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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.",
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Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis. / Nam, Bo Young; Park, Jung Tak; Kwon, Young Eun; Lee, Jung Pyo; Jung, Jong Ha; Kim, Youndong; Kim, Seonghun; Park, Jimin; Um, Jae Eun; Wu, Meiyan; Han, Seung Hyeok; Yoo, Tae Hyun; Kang, Shin Wook.

In: Molecular Therapy - Nucleic Acids, Vol. 7, 01.06.2017, p. 396-407.

Research output: Contribution to journalArticle

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T1 - Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis

AU - Nam, Bo Young

AU - Park, Jung Tak

AU - Kwon, Young Eun

AU - Lee, Jung Pyo

AU - Jung, Jong Ha

AU - Kim, Youndong

AU - Kim, Seonghun

AU - Park, Jimin

AU - Um, Jae Eun

AU - Wu, Meiyan

AU - Han, Seung Hyeok

AU - Yoo, Tae Hyun

AU - Kang, Shin Wook

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AB - 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.

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