Department of Nephrology, the First Hospital of Jilin University, Changchun, China.
Department of Obstetrics and Gynecology, the First Hospital of Jilin University, Changchun, China.
Diabetes Metab J. 2021 Nov;45(6):909-920. doi: 10.4093/dmj.2020.0168. Epub 2021 Jun 4.
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.
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.
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.
Our study demonstrates that the HDAC inhibitor SFN protects against diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7.
膳食补充剂萝卜硫素（SFN）已被报道可减少糖尿病引起的肾纤维化，并抑制组蛋白去乙酰化酶（HDAC）活性。骨形态发生蛋白 7（BMP-7）已被证明可减少转化生长因子-β1诱导的肾纤维化。本研究旨在探讨 SFN 对糖尿病诱导的肾纤维化中 BMP-7 表达的表观遗传作用。
链脲佐菌素（STZ）诱导的糖尿病小鼠和年龄匹配的对照小鼠皮下注射 SFN 或载体 4 个月，以测量 SFN 对肾脏的体内作用。人肾近端管状（HK11）细胞系用于体外模拟糖尿病条件。HK11 细胞被转染以过表达 HDAC2，并接受高糖/棕榈酸（HG/Pal）处理，以探讨 SFN 介导的对 HG/Pal 诱导的肾纤维化的保护作用中的表观遗传调节 BMP-7。
SFN 显著减轻了体内糖尿病引起的肾纤维化。在我们检测到的所有 HDAC 中，HDAC2 活性在 STZ 诱导的糖尿病肾脏和 HG/Pal 处理的 HK11 细胞中明显升高。SFN 抑制了糖尿病引起的 HDAC2 活性增加，这与组蛋白乙酰化和 BMP-7 启动子的转录激活有关。HDAC2 过表达降低了 BMP-7 的表达，并消除了 SFN 对 HG/Pal 诱导的纤维化的体外保护作用。
我们的研究表明，HDAC 抑制剂 SFN 通过 BMP-7 的表观遗传上调来保护糖尿病引起的肾纤维化。
