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Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions

Diabetic nephropathy, the major cause of chronic kidney disease, is associated with progressive renal fibrosis. Recently, accumulation of periostin, an extracellular matrix protein, was shown to augment renal fibrosis. Aptamers have higher binding affinities without developing the common side effect...

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Autores principales: Um, Jae Eun, Park, Jung Tak, Nam, Bo Young, Lee, Jung Pyo, Jung, Jong Ha, Kim, Youndong, Kim, Seonghun, Park, Jimin, Wu, Meiyan, Han, Seung Hyeok, Yoo, Tae-Hyun, Kang, Shin-Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561139/
https://www.ncbi.nlm.nih.gov/pubmed/28819200
http://dx.doi.org/10.1038/s41598-017-09238-6
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author Um, Jae Eun
Park, Jung Tak
Nam, Bo Young
Lee, Jung Pyo
Jung, Jong Ha
Kim, Youndong
Kim, Seonghun
Park, Jimin
Wu, Meiyan
Han, Seung Hyeok
Yoo, Tae-Hyun
Kang, Shin-Wook
author_facet Um, Jae Eun
Park, Jung Tak
Nam, Bo Young
Lee, Jung Pyo
Jung, Jong Ha
Kim, Youndong
Kim, Seonghun
Park, Jimin
Wu, Meiyan
Han, Seung Hyeok
Yoo, Tae-Hyun
Kang, Shin-Wook
author_sort Um, Jae Eun
collection PubMed
description Diabetic nephropathy, the major cause of chronic kidney disease, is associated with progressive renal fibrosis. Recently, accumulation of periostin, an extracellular matrix protein, was shown to augment renal fibrosis. Aptamers have higher binding affinities without developing the common side effects of antibodies. Thus, we evaluated the effect of periostin inhibition by an aptamer-based inhibitor on renal fibrosis under diabetic conditions. In vitro, transforming growth factor-β1 (TGF-β1) treatment significantly upregulated periostin, fibronectin, and type I collagen mRNA and protein expressions in inner medullary collecting duct (IMCD) cells. These increases were attenuated significantly in periostin-binding DNA aptamer (PA)-treated IMCD cells exposed to TGF-β1. In vivo, PA treatment attenuated the increased blood urea nitrogen levels in the diabetic mice significantly. Fibronectin and type I collagen mRNA and protein expressions increased significantly in the kidneys of diabetic mice: PA administration abrogated these increases significantly. Immunohistochemistry and Sirius Red staining also revealed that fibronectin expression was significantly higher and tubulointersititial fibrosis was significantly worse in diabetic mice kidneys compared with control mice. These changes were ameliorated by PA treatment. These findings suggested that inhibition of periostin using a DNA aptamer could be a potential therapeutic strategy against renal fibrosis in diabetic nephropathy.
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spelling pubmed-55611392017-08-18 Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions Um, Jae Eun Park, Jung Tak Nam, Bo Young Lee, Jung Pyo Jung, Jong Ha Kim, Youndong Kim, Seonghun Park, Jimin Wu, Meiyan Han, Seung Hyeok Yoo, Tae-Hyun Kang, Shin-Wook Sci Rep Article Diabetic nephropathy, the major cause of chronic kidney disease, is associated with progressive renal fibrosis. Recently, accumulation of periostin, an extracellular matrix protein, was shown to augment renal fibrosis. Aptamers have higher binding affinities without developing the common side effects of antibodies. Thus, we evaluated the effect of periostin inhibition by an aptamer-based inhibitor on renal fibrosis under diabetic conditions. In vitro, transforming growth factor-β1 (TGF-β1) treatment significantly upregulated periostin, fibronectin, and type I collagen mRNA and protein expressions in inner medullary collecting duct (IMCD) cells. These increases were attenuated significantly in periostin-binding DNA aptamer (PA)-treated IMCD cells exposed to TGF-β1. In vivo, PA treatment attenuated the increased blood urea nitrogen levels in the diabetic mice significantly. Fibronectin and type I collagen mRNA and protein expressions increased significantly in the kidneys of diabetic mice: PA administration abrogated these increases significantly. Immunohistochemistry and Sirius Red staining also revealed that fibronectin expression was significantly higher and tubulointersititial fibrosis was significantly worse in diabetic mice kidneys compared with control mice. These changes were ameliorated by PA treatment. These findings suggested that inhibition of periostin using a DNA aptamer could be a potential therapeutic strategy against renal fibrosis in diabetic nephropathy. Nature Publishing Group UK 2017-08-17 /pmc/articles/PMC5561139/ /pubmed/28819200 http://dx.doi.org/10.1038/s41598-017-09238-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Um, Jae Eun
Park, Jung Tak
Nam, Bo Young
Lee, Jung Pyo
Jung, Jong Ha
Kim, Youndong
Kim, Seonghun
Park, Jimin
Wu, Meiyan
Han, Seung Hyeok
Yoo, Tae-Hyun
Kang, Shin-Wook
Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions
title Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions
title_full Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions
title_fullStr Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions
title_full_unstemmed Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions
title_short Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions
title_sort periostin-binding dna aptamer treatment attenuates renal fibrosis under diabetic conditions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561139/
https://www.ncbi.nlm.nih.gov/pubmed/28819200
http://dx.doi.org/10.1038/s41598-017-09238-6
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