Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism

Background/Aims: Diabetic nephropathy is the one of the most serious microvascular complications of diabetes mellitus, and “metabolic memory” plays a vital role in the development of diabetic complications. To investigate the effect of epigenetics on metabolic memory, we analyzed the impact of trans...

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Main Authors: Deng Yunlei, Fan  Qiuling, Wang Xu, Zhao Qianwen, Cao Xu, Xu Li, Wang Lining
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2018-09-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:https://www.karger.com/Article/FullText/493619
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author Deng Yunlei
Fan  Qiuling
Wang Xu
Zhao Qianwen
Cao Xu
Xu Li
Wang Lining
author_facet Deng Yunlei
Fan  Qiuling
Wang Xu
Zhao Qianwen
Cao Xu
Xu Li
Wang Lining
author_sort Deng Yunlei
collection DOAJ
description Background/Aims: Diabetic nephropathy is the one of the most serious microvascular complications of diabetes mellitus, and “metabolic memory” plays a vital role in the development of diabetic complications. To investigate the effect of epigenetics on metabolic memory, we analyzed the impact of transient high-glucose stimulation on the secretion of inflammatory factors from rat glomerular mesangial cells. Methods: Rat glomerular mesangial cells (HBZY-1) were divided into three groups: high-glucose group (25 mM glucose), hypertonic group (5.5 mM glucose+19.5 mM mannitol), and normal-glucose control group (5.5 mM glucose). Mesangial cells were cultured in high-glucose, hypertonic, and normal-glucose media for 24 h and transitioned to normal-glucose culture for 24, 48, and 72 h. Then, protein, mRNA, and supernatants were harvested. The expression of monomethylated H3K4 was determined by western blot analysis, and the expression of the NF-κB subunit p65 and histone methyltransferase set7/9 was determined by quantitative real-time PCR. The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) was detected by an enzyme-linked immunosorbent assay. Results: Compared with the control group, H3K4me1 expression was upregulated after transient high-glucose stimulation, gradually downregulated in the following 48 h (P < 0.05), and reached the level of the control group at 72 h (P > 0.05). The expression of set7/9 was increased after 24 h of high-glucose stimulation and the following 24 h and 48 h (P < 0.05); it then returned to the level of the control group at 72 h. Compared with the control group, the increased expression of p65, VCAM-1, and MCP-1 was sustained for at least 72 h in the high-glucose group. Conclusion: Transient high-glucose stimulation can induce the persistent secretion of inflammatory factors from rat glomerular mesangial cells via histone modification.
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spelling doaj.art-fd2f544983cd44c58e80381c6a9596dc2022-12-22T00:55:42ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-09-014951747175410.1159/000493619493619Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic MechanismDeng YunleiFan  QiulingWang XuZhao QianwenCao XuXu LiWang LiningBackground/Aims: Diabetic nephropathy is the one of the most serious microvascular complications of diabetes mellitus, and “metabolic memory” plays a vital role in the development of diabetic complications. To investigate the effect of epigenetics on metabolic memory, we analyzed the impact of transient high-glucose stimulation on the secretion of inflammatory factors from rat glomerular mesangial cells. Methods: Rat glomerular mesangial cells (HBZY-1) were divided into three groups: high-glucose group (25 mM glucose), hypertonic group (5.5 mM glucose+19.5 mM mannitol), and normal-glucose control group (5.5 mM glucose). Mesangial cells were cultured in high-glucose, hypertonic, and normal-glucose media for 24 h and transitioned to normal-glucose culture for 24, 48, and 72 h. Then, protein, mRNA, and supernatants were harvested. The expression of monomethylated H3K4 was determined by western blot analysis, and the expression of the NF-κB subunit p65 and histone methyltransferase set7/9 was determined by quantitative real-time PCR. The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) was detected by an enzyme-linked immunosorbent assay. Results: Compared with the control group, H3K4me1 expression was upregulated after transient high-glucose stimulation, gradually downregulated in the following 48 h (P < 0.05), and reached the level of the control group at 72 h (P > 0.05). The expression of set7/9 was increased after 24 h of high-glucose stimulation and the following 24 h and 48 h (P < 0.05); it then returned to the level of the control group at 72 h. Compared with the control group, the increased expression of p65, VCAM-1, and MCP-1 was sustained for at least 72 h in the high-glucose group. Conclusion: Transient high-glucose stimulation can induce the persistent secretion of inflammatory factors from rat glomerular mesangial cells via histone modification.https://www.karger.com/Article/FullText/493619Diabetic NephropathyHistone MethylationMetabolic MemoryInflammatory FactorsEpigenetics
spellingShingle Deng Yunlei
Fan  Qiuling
Wang Xu
Zhao Qianwen
Cao Xu
Xu Li
Wang Lining
Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism
Cellular Physiology and Biochemistry
Diabetic Nephropathy
Histone Methylation
Metabolic Memory
Inflammatory Factors
Epigenetics
title Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism
title_full Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism
title_fullStr Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism
title_full_unstemmed Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism
title_short Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism
title_sort transient high glucose stimulation induces persistent inflammatory factor secretion from rat glomerular mesangial cells via an epigenetic mechanism
topic Diabetic Nephropathy
Histone Methylation
Metabolic Memory
Inflammatory Factors
Epigenetics
url https://www.karger.com/Article/FullText/493619
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