Abstract | OBJECTIVE: METHODS: Diabetes was induced in ApoC3 transgenic (Tg) and knockout (KO) mice by injection of streptozotocin. We studied the effect of ApoC3 on type 1 DN after 4 months of diabetes. Plasma glucose and lipid levels, renal function parameters and inflammation- and fibrogenesis-related gene and protein expression levels were studied. In vitro, human mesangial cells (HMCs) were incubated with high levels of glucose or/and triglyceride-rich lipoproteins (TRLs) with a high or low ApoC3 content isolated from Tg or wild-type (WT) mice, respectively, to explore the mechanisms of ApoC3 on development of DN. RESULTS: We found that compared to WT mice, Tg mice exhibited hypertriglyceridemia (HTG), aggravated early renal function injury and inflammation, enlarged glomerular and mesangial surface areas, renal lipid deposition and elevated fibrogenesis-related gene expression levels after 4 months of diabetes. ApoC3 overexpression activated the renal Toll-like receptor 2 (TLR2) and nuclear factor-κB (NF-κB) signaling pathways and increased the renal gene and protein expression levels of the downstream inflammatory factors TNF-α, VCAM-1 and MCP-1. Unfortunately, we did not find that ApoC3 deficiency had an obvious protective effect against DN. In vitro, we found that TRLs with a high ApoC3 content increased the gene and protein expression levels of inflammation- and fibrogenesis-related factors in HMCs compared to those following administration of the same concentration of TRLs with a low ApoC3 content. These effects of ApoC3 were inhibited by blockade of TLR2 or NF-κB. CONCLUSIONS: These findings suggest that ApoC3 aggravates early-stage DN by activating the renal TLR2/NF-κB pathway which is partially independent of HTG.
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Authors | Huan Wang, Xiaomin Huang, Pengfei Xu, Xuejing Liu, Zihao Zhou, Fuhua Wang, Jingyi Li, Yuhui Wang, Xunde Xian, George Liu, Wei Huang |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 119
Pg. 154740
(06 2021)
ISSN: 1532-8600 [Electronic] United States |
PMID | 33639183
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 Elsevier Inc. All rights reserved. |
Chemical References |
- Apolipoprotein C-III
- NF-kappa B
- Toll-Like Receptor 2
- Streptozocin
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Topics |
- Animals
- Apolipoprotein C-III
(genetics, physiology)
- Cells, Cultured
- Diabetes Mellitus, Experimental
(chemically induced, genetics, metabolism)
- Diabetes Mellitus, Type 1
(complications, genetics, metabolism)
- Diabetic Nephropathies
(genetics, metabolism, pathology)
- Disease Progression
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Transgenic
- NF-kappa B
(metabolism)
- Signal Transduction
(genetics)
- Streptozocin
- Toll-Like Receptor 2
(metabolism)
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