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Quercetin suppresses NF-κB and MCP-1 expression in a high glucose-induced human mesangial cell proliferation model
Pin Chen1, Qiyang Shi, Xiangjin Xu
1Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian 350025, P.R. China.
Abstract:
Diabetic nephropathy (DN), which is characterized by mesangial cell proliferation, is a common complication observed in diabetic patients. The protective effects of quercetin for DN have been reported; however, the mechanism has yet to be determined. We aimed to identify the underlying mechanism for quercetin protection against DN. High glucose (HG)-induced human mesangial cell (HMC) proliferation, a feature of the early stages of diabetic nephropathy, was employed as an in vitro model. Cells were grown in normal glucose (5.6 mM), high glucose (30 mM) or high glucose with various concentrations of quercetin. Cell proliferation, cell cycle progression, and expression of NF-κB and MCP-1 were examined by MTT assay, DNA staining, immunocytochemistry and western blot analysis, respectively. HMCs cultured in high glucose had signficantly greater proliferation, accumulation in the G1 phase, upregulated NF-κB and MCP-1 expression. Quercetin treatment reversed the effects of high glucose in a dose-dependent manner. Cotreatment of quercetin with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB activation, suggest that the effects of quercetin are partially mediated by NF-κB signaling. Quercetin partially suppresses the effects of high glucose in HMC cultures, which are mediated at least in part through the suppression of NF-κB.
Insights
Quercetin protects against diabetic nephropathy (DN) by inhibiting high glucose-induced human mesangial cell proliferation. Its protective effects are linked to the suppression of NF-κB signaling pathways.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Diabetic nephropathy (DN) is a common diabetes complication characterized by mesangial cell proliferation.
- The protective mechanisms of quercetin against DN remain unclear.
Purpose of the Study:
- To elucidate the underlying mechanism of quercetin's protective effects against diabetic nephropathy.
- To investigate quercetin's impact on high glucose-induced human mesangial cell (HMC) proliferation and associated molecular pathways.
Main Methods:
- An in vitro model using high glucose (HG)-induced HMC proliferation.
- Assessment of cell proliferation, cell cycle, and expression of NF-κB and MCP-1.
- Utilized MTT assay, DNA staining, immunocytochemistry, and western blot analysis.
Main Results:
- High glucose significantly increased HMC proliferation, G1 phase accumulation, and upregulated NF-κB and MCP-1 expression.
- Quercetin treatment dose-dependently reversed these high glucose-induced effects.
- Inhibition of NF-κB activation with PDTC suggested quercetin's effects are partially mediated by NF-κB signaling.
Conclusions:
- Quercetin demonstrates protective effects against high glucose-induced mesangial cell proliferation.
- These protective effects are, at least in part, mediated through the suppression of NF-κB signaling.
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