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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article number8490
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Nucleotide Aptamers
Fibrosis
Kidney
Fibronectins
Diabetic Nephropathies
Transforming Growth Factors
Collagen Type I
Therapeutics
Messenger RNA
Extracellular Matrix Proteins
Blood Urea Nitrogen
Chronic Renal Insufficiency
Proteins
Immunohistochemistry
Staining and Labeling
Antibodies

All Science Journal Classification (ASJC) codes

  • General

Cite this

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. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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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.

In: Scientific reports, Vol. 7, No. 1, 8490, 01.12.2017.

Research output: Contribution to journalArticle

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AU - Um, Jae Eun

AU - Park, Jung Tak

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AU - Kim, Youndong

AU - Kim, Seonghun

AU - Park, Jimin

AU - Wu, Meiyan

AU - Han, Seung Hyeok

AU - Yoo, Tae Hyun

AU - Kang, Shin Wook

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