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Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis
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 de...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436072/ https://www.ncbi.nlm.nih.gov/pubmed/28624215 http://dx.doi.org/10.1016/j.omtn.2017.05.001 |
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author | 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 |
author_facet | 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 |
author_sort | Nam, Bo Young |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5436072 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-54360722017-05-31 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 Mol Ther Nucleic Acids Original Article 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. American Society of Gene & Cell Therapy 2017-05-08 /pmc/articles/PMC5436072/ /pubmed/28624215 http://dx.doi.org/10.1016/j.omtn.2017.05.001 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article 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 |
title | Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis |
title_full | Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis |
title_fullStr | Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis |
title_full_unstemmed | Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis |
title_short | Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis |
title_sort | periostin-binding dna aptamer treatment ameliorates peritoneal dialysis-induced peritoneal fibrosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436072/ https://www.ncbi.nlm.nih.gov/pubmed/28624215 http://dx.doi.org/10.1016/j.omtn.2017.05.001 |
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