Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7

Background The dietary agent sulforaphane (SFN) has been reported to reduce diabetes-induced renal fibrosis, as well as inhibit histone deacetylase (HDAC) activity. Bone morphologic protein 7 (BMP-7) has been shown to reduce renal fibrosis induced by transforming growth factor-beta1. The aim of this...

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Autores principales:	Lili Kong, Hongyue Wang, Chenhao Li, Huiyan Cheng, Yan Cui, Li Liu, Ying Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Korean Diabetes Association 2021
Materias:	bone morphogenetic protein 7 diabetic nephropathies histone deacetylase 2 sulforafan Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/aa71d2dc0dc64f388810ccd4f18dfbc4
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spelling	oai:doaj.org-article:aa71d2dc0dc64f388810ccd4f18dfbc42021-12-01T05:07:51ZSulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-72233-60792233-608710.4093/dmj.2020.0168https://doaj.org/article/aa71d2dc0dc64f388810ccd4f18dfbc42021-11-01T00:00:00Zhttp://www.e-dmj.org/upload/pdf/dmj-2020-0168.pdfhttps://doaj.org/toc/2233-6079https://doaj.org/toc/2233-6087Background The dietary agent sulforaphane (SFN) has been reported to reduce diabetes-induced renal fibrosis, as well as inhibit histone deacetylase (HDAC) activity. Bone morphologic protein 7 (BMP-7) has been shown to reduce renal fibrosis induced by transforming growth factor-beta1. The aim of this study was to investigate the epigenetic effect of SFN on BMP-7 expression in diabetes-induced renal fibrosis. Methods Streptozotocin (STZ)-induced diabetic mice and age-matched controls were subcutaneously injected with SFN or vehicle for 4 months to measure the in vivo effects of SFN on the kidneys. The human renal proximal tubular (HK11) cell line was used to mimic diabetic conditions in vitro. HK11 cells were transfected to over-express HDAC2 and treated with high glucose/palmitate (HG/Pal) to explore the epigenetic modulation of BMP-7 in SFN-mediated protection against HG/Pal-induced renal fibrosis. Results SFN significantly attenuated diabetes-induced renal fibrosis in vivo. Among all of the HDACs we detected, HDAC2 activity was markedly elevated in the STZ-induced diabetic kidneys and HG/Pal-treated HK11 cells. SFN inhibited the diabetes-induced increase in HDAC2 activity which was associated with histone acetylation and transcriptional activation of the BMP-7 promoter. HDAC2 over-expression reduced BMP-7 expression and abolished the SFN-mediated protection against HG/Pal-induced fibrosis in vitro. Conclusion Our study demonstrates that the HDAC inhibitor SFN protects against diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7.Lili KongHongyue WangChenhao LiHuiyan ChengYan CuiLi LiuYing ZhaoKorean Diabetes Associationarticlebone morphogenetic protein 7diabetic nephropathieshistone deacetylase 2sulforafanDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENDiabetes & Metabolism Journal, Vol 45, Iss 6, Pp 909-920 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone morphogenetic protein 7 diabetic nephropathies histone deacetylase 2 sulforafan Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	bone morphogenetic protein 7 diabetic nephropathies histone deacetylase 2 sulforafan Diseases of the endocrine glands. Clinical endocrinology RC648-665 Lili Kong Hongyue Wang Chenhao Li Huiyan Cheng Yan Cui Li Liu Ying Zhao Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7
description	Background The dietary agent sulforaphane (SFN) has been reported to reduce diabetes-induced renal fibrosis, as well as inhibit histone deacetylase (HDAC) activity. Bone morphologic protein 7 (BMP-7) has been shown to reduce renal fibrosis induced by transforming growth factor-beta1. The aim of this study was to investigate the epigenetic effect of SFN on BMP-7 expression in diabetes-induced renal fibrosis. Methods Streptozotocin (STZ)-induced diabetic mice and age-matched controls were subcutaneously injected with SFN or vehicle for 4 months to measure the in vivo effects of SFN on the kidneys. The human renal proximal tubular (HK11) cell line was used to mimic diabetic conditions in vitro. HK11 cells were transfected to over-express HDAC2 and treated with high glucose/palmitate (HG/Pal) to explore the epigenetic modulation of BMP-7 in SFN-mediated protection against HG/Pal-induced renal fibrosis. Results SFN significantly attenuated diabetes-induced renal fibrosis in vivo. Among all of the HDACs we detected, HDAC2 activity was markedly elevated in the STZ-induced diabetic kidneys and HG/Pal-treated HK11 cells. SFN inhibited the diabetes-induced increase in HDAC2 activity which was associated with histone acetylation and transcriptional activation of the BMP-7 promoter. HDAC2 over-expression reduced BMP-7 expression and abolished the SFN-mediated protection against HG/Pal-induced fibrosis in vitro. Conclusion Our study demonstrates that the HDAC inhibitor SFN protects against diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7.
format	article
author	Lili Kong Hongyue Wang Chenhao Li Huiyan Cheng Yan Cui Li Liu Ying Zhao
author_facet	Lili Kong Hongyue Wang Chenhao Li Huiyan Cheng Yan Cui Li Liu Ying Zhao
author_sort	Lili Kong
title	Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7
title_short	Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7
title_full	Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7
title_fullStr	Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7
title_full_unstemmed	Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7
title_sort	sulforaphane ameliorates diabetes-induced renal fibrosis through epigenetic up-regulation of bmp-7
publisher	Korean Diabetes Association
publishDate	2021
url	https://doaj.org/article/aa71d2dc0dc64f388810ccd4f18dfbc4
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Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7

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