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

Lili Kong; Hongyue Wang; Chenhao Li; Huiyan Cheng; Yan Cui; Li Liu; Ying Zhao

doi:10.4093/dmj.2020.0168

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자료유형: 학술저널

저자정보: Lili Kong (the First Hospital of Jilin University) Hongyue Wang (the First Hospital of Jilin University) Chenhao Li (the First Hospital of Jilin University) Huiyan Cheng (the First Hospital of Jilin University) Yan Cui (the First Hospital of Jilin University) Li Liu (the First Hospital of Jilin University) Ying Zhao (the First Hospital of Jilin University)

저널정보: 대한당뇨병학회 Diabetes and Metabolism Journal Diabetes and Metabolism Journal Vol.45 No.6

발행연도: 2021.11

수록면: 909 - 920 (12page)

DOI: 10.4093/dmj.2020.0168

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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.

#Bone morphogenetic protein 7 #Diabetic nephropathies #Histone deacetylase 2 #Sulforafan

참고문헌 (39)

참고문헌 신청

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Hakami NY / 2016 / Trichostatin A, a histone deacetylase inhibitor suppresses NADPH oxidase 4-derived redox signalling and angiogenesis / J Cell Mol Med 20:1932~1944

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