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

Abstract 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 si...

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Autores principales:	Jae Eun Um, Jung Tak Park, Bo Young Nam, Jung Pyo Lee, Jong Ha Jung, Youndong Kim, Seonghun Kim, Jimin Park, Meiyan Wu, Seung Hyeok Han, Tae-Hyun Yoo, Shin-Wook Kang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77c5a019a95947a5bb0ff5e5ccee3d7d
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spelling	oai:doaj.org-article:77c5a019a95947a5bb0ff5e5ccee3d7d2021-12-02T15:05:21ZPeriostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions10.1038/s41598-017-09238-62045-2322https://doaj.org/article/77c5a019a95947a5bb0ff5e5ccee3d7d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09238-6https://doaj.org/toc/2045-2322Abstract 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.Jae Eun UmJung Tak ParkBo Young NamJung Pyo LeeJong Ha JungYoundong KimSeonghun KimJimin ParkMeiyan WuSeung Hyeok HanTae-Hyun YooShin-Wook KangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jae Eun Um Jung Tak Park Bo Young Nam Jung Pyo Lee Jong Ha Jung Youndong Kim Seonghun Kim Jimin Park Meiyan Wu Seung Hyeok Han Tae-Hyun Yoo Shin-Wook Kang Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions
description	Abstract 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.
format	article
author	Jae Eun Um Jung Tak Park Bo Young Nam Jung Pyo Lee Jong Ha Jung Youndong Kim Seonghun Kim Jimin Park Meiyan Wu Seung Hyeok Han Tae-Hyun Yoo Shin-Wook Kang
author_facet	Jae Eun Um Jung Tak Park Bo Young Nam Jung Pyo Lee Jong Ha Jung Youndong Kim Seonghun Kim Jimin Park Meiyan Wu Seung Hyeok Han Tae-Hyun Yoo Shin-Wook Kang
author_sort	Jae Eun Um
title	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_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_sort	periostin-binding dna aptamer treatment attenuates renal fibrosis under diabetic conditions
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/77c5a019a95947a5bb0ff5e5ccee3d7d
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Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions

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