scholarly journals Effects of Qijin granules on high glucose-induced proliferation, apoptosis and expression of nuclear factor- κB and MCP-1 in rat glomerular mesangial cells

2021 ◽  
Vol 20 (9) ◽  
pp. 1819-1826
Author(s):  
Yuanfeng Yang ◽  
Gaocai Xiong ◽  
Renhui Yang ◽  
Yuchuan Li ◽  
Yuling Luo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Glucose ◽  
Mesangial Cells ◽  
Control Group ◽  
Glomerular Mesangial Cells ◽  
Smad Signaling ◽  
Apoptosis Rate ◽  
Proliferation And Apoptosis ◽  
Protein Expressions ◽  
Tgf Β1

Purpose: To investigate the effects of Qijin granules on high glucose-induced proliferation and apoptosis in rat glomerular mesangial cells (MC).Methods: MC cells from rats were passaged and cultured, and randomly divided into control group (CNG), high glucose group (HGG), Western medicine group (WMG, high glucose + Benazepril + Gliquidone), and Qijin granules 1/2/3 group (high glucose + different doses of Qijin granules). Mesangial cells proliferation was measured using MTT assay. The NF-κB, MCP-1 and inflammatory factors in supernatant were determined by ELISA. Apoptosis rate and cell cycle were assessed by flow cytometry. The apoptosis-related TGF-β1/Smad signaling pathway-related protein expressions were measured by Western blot.Results: The A-value and early apoptosis rate, apoptosis rate and S-phase percentage, and protein expressions of NF-κB, MCP-1, IL-6, IL-2, TNF-ɑ, Bax, Cyt-C, caspase-3, TGF-β1, and p-Smad3 of MC cells in the HGG at 12 h, 24 h and 48 h were higher than those in the CNG. The above indices were lower in the WMG, and Qijin granules 1/2/3 groups than in the HGG. The Bcl-2, Smad7 protein expression level and the percentage of G1 and G2/M phase were lower in the HGG than in the CNG, and the above indeices were higher in the WMG and Qijin granules 1/2/3 group than in HGG.Conclusion: Qijin granules can dose-dependently inhibit high glucose-induced proliferation and apoptosis in rat MC cells, block the cell cycle and reduce inflammatory responses. This may be related to the regulation of NF-κB, MCP-1 and TGF-β1/Smad signaling pathways. These findings provide theoretical and experimental basis for the clinical treatment of early diabetic nephropathy.

Exosomes from high glucose–treated macrophages activate glomerular mesangial cells via TGF‐β1/Smad3 pathway in vivo and in vitro

2019 ◽  
Vol 33 (8) ◽  
pp. 9279-9290 ◽  
Author(s):  
Qi‐Jin Zhu ◽  
Mei Zhu ◽  
Xing‐Xin Xu ◽  
Xiao‐Ming Meng ◽  
Yong‐Gui Wu
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Tgf Β1

Ganglioside GM3 inhibits the high glucose- and TGF-β1-induced proliferation of rat glomerular mesangial cells

Life Sciences ◽  
2005 ◽  
Vol 77 (20) ◽  
pp. 2540-2551 ◽  
Author(s):  
Dong Hoon Kwak ◽  
Seoul Lee ◽  
Sung Jo Kim ◽  
Seon Ho Ahn ◽  
Ju Hung Song ◽  
...  
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Ganglioside Gm3 ◽  
Tgf Β1

scholarly journals Influence of glucosamine on glomerular mesangial cell turnover: implications for hyperglycemia and hexosamine pathway flux

2010 ◽  
Vol 298 (2) ◽  
pp. E210-E221 ◽  
Author(s):  
Leighton R. James ◽  
Catherine Le ◽  
James W. Scholey
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Mammalian Target Of Rapamycin ◽  
Nuclear Antigen ◽  
Glomerular Mesangial Cells ◽  
Glomerular Mesangial Cell ◽  
Low Concentrations ◽  
Hexosamine Pathway ◽  
Proliferation And Apoptosis ◽  
M Phase

Cells exposed to high glucose may undergo hypertrophy, proliferation, and apoptosis, but the role of hexosamine flux in mediating these effects has not been fully elucidated. Accordingly, we studied the effects of glucose and glucosamine on rat glomerular mesangial cells (MC) turnover. Compared with physiological glucose (5.6 mM), treatment with high glucose (25 mM) for 24 h stimulated MC proliferation, an effect that was mimicked by exposure to low concentrations of glucosamine (0.05 mM). The percentage of cells in G0/G1 phase of the cell cycle was reduced with a concomitant increase of the number of cells in G2/M phase. Proliferating cell nuclear antigen, phosphorylated mammalian target of rapamycin [phospho-mTOR (Ser2448)], and total regulatory-associated protein of mTOR were increased by high glucose and glucosamine treatment. Inhibition of glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate-limiting enzyme for hexosamine flux, with 6-diazo-5-oxonorleucine (10 μM) and of mTOR with rapamycin both attenuated glucose-mediated MC proliferation. Higher glucosamine concentrations (0.25–10 mM) caused MC apoptosis after 48 h, and, in addition, GFAT overexpression also increased MC apoptosis (TdT-dUTP nick end-labeling-positive cells: 3.8 ± 0.3 vs. 1.1 ± 0.2% for empty vector; P < 0.05). Hence, hexosamine flux is an important determinant of MC proliferation and apoptosis. The proliferative response to high glucose and hexosamine flux is rapamycin-sensitive, suggesting that this effect is associated with signaling through rapamycin-sensitive mTOR complex 1 (mTORC1).

scholarly journals Trigonelline regulates Wnt/β-catenin signaling in glomerular mesangial cells under high glucose conditions

2021 ◽  
Author(s):  
Chen Chen ◽  
Yan Shi ◽  
Zhen Chen ◽  
Xiangjun Li ◽  
Bo Sun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
High Glucose ◽  
Cell Cycle Progression ◽  
Cell Injury ◽  
Mesangial Cells ◽  
Animal Experiments ◽  
Glomerular Mesangial Cells ◽  
Glucose Levels ◽  
Elevated Glucose

Abstract Background: Trigonelline have hypoglycemic effects. In previous animal experiments, we observed that trigonelline (TRL) treat-ment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced rats, TRL treatment reduced albuminuria, lowered blood sugar, improved renal function and alleviated the pathological alterations within the glomerulus. Methods: We stimulated human mesangial cells (HMC) with high glucose (30 mmol / L) medium. HMCs were transfected with β-catenin plasmid or siRNA to investigate the effect of trigonelline on high glucose-induced excessive proliferation and apoptosis of HMCs, and to understand its mechanism of action. Cell viability was measured by MTT assay. Flow cytometry was used to detect the cell cycle. Cell apoptosis was evaluated by flow cytometry and terminal dUTP transferase nick end labeling (TUNEL) assay. Protein and mRNA expression of β-catenin, Wnt5a, TCF4, Cyclin D1, and CDK4 were detected by western blotting and RT-PCR, respectively. Results: Trigonelline inhibited cell proliferation by blocking cell-cycle progression at the G1 phase and decreased apoptosis via the Wnt/β-catenin pathway. Elevated glucose levels enhanced the expression of β-catenin, an important modulator of diabetic nephropathy, while trigonelline restored up-regulation. Conclusions: High glucose and high expression of β-catenin could lead to cell injury; however, this effect was mitigated by trigonelline via managing the canonical Wnt/β-catenin signaling pathway.

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

2018 ◽  
Vol 49 (5) ◽  
pp. 1747-1754 ◽  
Author(s):  
Deng Yunlei ◽  
Fan  Qiuling ◽  
Wang Xu ◽  
Zhao Qianwen ◽  
Cao Xu ◽  
...  
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Inflammatory Factors ◽  
Control Group ◽  
Metabolic Memory ◽  
Glomerular Mesangial Cells ◽  
Glucose Stimulation ◽  
Normal Glucose ◽  
High Glucose Group ◽  
Glucose Group

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.

scholarly journals Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells

2015 ◽  
Vol 36 (6) ◽  
pp. 2093-2107 ◽  
Author(s):  
Dan Wang ◽  
Mei-Ping Guan ◽  
Zong-Ji Zheng ◽  
Wen-Qi Li ◽  
Fu-Ping Lyv ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
High Glucose ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Protein Levels ◽  
Oletf Rats ◽  
Type Iv ◽  
Regulated Expression ◽  
Stage Renal Disease ◽  
Tgf Β1

Backgroud: Diabetic nephropathy is one of the most frequent causes of end-stage renal disease and is associated with proliferation of glomerular mesangial cells (MCs) and excessive production of the extracellular matrix (ECM). Several studies have shown that early growth response factor 1 (Egr1) plays a key role in renal fibrosis by regulating the expression of genes encoding ECM components. However, whether Egr1 also contributes to diabetic nephropathy is unclear. Methods: In the present study, we compared the expression of Egr1 in kidneys from OLETF rats with spontaneous type 2 diabetes and healthy LETO rats. We also examined whether high glucose and TGF-β1 signaling up-regulated Egr1 expression in cultured MCs, and whether Egr1 expression influenced MC proliferation and expression of ECM genes. Results: We found that higher expression of Egr1 and TGF-β1, at both the mRNA and protein levels, the kidneys from OLETF rats vs. LETO rats. High glucose or TGF-β1 signaling rapidly up-regulated expression of Egr1 mRNA and protein in cultured MCs. Overexpressing Egr1 in MCs by transfection with M61-Egr1 plasmid or treatment with high glucose up-regulated expression of fibronectin, type IV collagen and TGF-β1, and promoted MC proliferation. Conversely, siRNA-mediated silencing of Egr1 expression down-regulated these genes and inhibited MC proliferation. Chromatin immunoprecipitation (ChIP) assays revealed that Egr1 bound to the TGF-β1 promoter. Conclusion: Our results provide strong evidence that Egr1 contributes to diabetic nephropathy by enhancing MC proliferation and ECM production, in part by interacting with TGF-β1.

scholarly journals Reduced β2GPI Inhibiting Glomerular Mesangial Cells VEGF-NO Axis Uncoupling Induced by High Glucose

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Zhou Saijun ◽  
Li Xin ◽  
Wang Jie ◽  
Xiao Shumin ◽  
Liu Shuaihui ◽  
...  
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Control Group ◽  
Glomerular Mesangial Cells ◽  
Vegf Mrna ◽  
Dimer Formation ◽  
Glomerular Mesangial Cell ◽  
Vegf Signaling ◽  
Related Proteins ◽  
Vegf Signaling Pathway

VEGF-NO axis uncoupling is an important pathogenesis for DN. Reduced β2GPI could play a part in VEGF signaling pathway and has a protective effect on diabetic vascular disease. This study investigates the effect of reduced β2GPI on glomerular mesangial cells VEGF-NO axis uncoupling induced by high glucose. Compared to control group, glomerular mesangial cell line HBZY-1 cells treated with high glucose expressed higher levels of VEGF mRNA and protein and produced more ROS but less NO. The related proteins related to VEGF-NO axis were assayed. High glucose could significantly increase the expression of the level of VEGFR2 and obviously increase phosphorylation of Akt and eNOS but significantly decrease the expression of GTP cyclohydrolase 1 (GCH-1), reducing the production of eNOS dimer. Both β2GPI and reduced β2GPI partly reverse these effects caused by high glucose. Reduced β2GPI had stronger effect than β2GPI. GCH-1 is the speed limit of tetrahydrobiopterin (BH4) synthesis enzyme. As the key part of eNOS cofactors, BH4 could partly restore eNOS dimer induced by high glucose. Our results indicated that high glucose could interfere with eNOS dimer formation. β2GPI and reduced β2GPI can partly reverse the VEGF-NO axis uncoupling by restoring the GCH-1 expression level and then promote eNOS dimer formation.

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