235-OR: Sphingosine Kinase 2-Mediated Pyroptosis of Renal Tubular Epithelial Cells Contributes to the Progression of Diabetic Nephropathy

Diabetic nephropathy is considered one of the most common microvascular complications of diabetes and the pathophysiology involves multiple factors. Progressive diabetic nephropathy is believed to be related to the structure and function of the tubular epithelial cells in the kidney. However, the role of lysine acetylation in lesions of the renal tubular epithelial cells arising from hyperglycemia is poorly understood. Consequently, in this study, we cultured mouse renal tubular epithelial cells in vitro under high glucose conditions and analyzed the acetylation levels of proteins by liquid chromatography-high-resolution mass spectrometry. We identified 48 upregulated proteins and downregulated 86 proteins. In addition, we identified 113 sites with higher acetylation levels and 374 sites with lower acetylation levels. Subcellular localization analysis showed that the majority of the acetylated proteins were located in the mitochondria (43.17%), nucleus (28.57%) and cytoplasm (16.19%). Enrichment analysis indicated that these acetylated proteins are primarily associated with oxidative phosphorylation, the citrate cycle (TCA cycle), metabolic pathways and carbon metabolism. In addition, we used the MCODE plug-in and the cytoHubba plug-in in Cytoscape software to analyze the PPI network and displayed the first four most compact MOCDEs and the top 10 hub genes from the differentially expressed proteins between global and acetylated proteomes. Finally, we extracted 37 conserved motifs from 4915 acetylated peptides. Collectively, this comprehensive analysis of the proteome reveals novel insights into the role of lysine acetylation in tubular epithelial cells and may make a valuable contribution towards the identification of the pathological mechanisms of diabetic nephropathy.

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Inhibitory Effect of Gliquidone on Epithelial-to-Mesenchymal-Transition of Renal Tubular Epithelial Cells Under Diabetic Nephropathy Mouse Model

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2870 ◽

2022 ◽

Vol 12 (1) ◽

pp. 71-80

Author(s):

Ting Liu ◽

Jie Chen ◽

Yiying Ying ◽

Ling Shi ◽

Zhengyue Chen

Keyword(s):

Diabetic Nephropathy ◽

Epithelial Cells ◽

Body Mass ◽

Renal Fibrosis ◽

Epithelial To Mesenchymal Transition ◽

Inhibitory Effect ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Mesenchymal Transition ◽

Renal Tubular

This research aimed to study the inhibitory effect of Glurenorm (gliquidone) on epithelial-to-mesenchymal-transition (EMT) of renal tubular epithelial cells based on the diabetic nephropathy (DN) model. In this study, 30 specific pathogen-free (SPF) mice were selected to construct DN model and randomly rolled into groups A, B, and C, with 10 mice in each group. Low-dose, mediumdose, and high-dose Glurenorm were administered intragastrically. The results showed that the serum urea nitrogen content (7.23±0.39 mmol/L, 6.18±0.46 mmol/L) of control and C group was considerably inferior to A group (8.01±0.48 mmol/L), and the content of C group was greatly lower than controls (P < 0.05). The creatinine clearance rate (2.97±0.44 mL/min, 4.02±0.31 mL/min) of mice in control and C group was notably superior to A group (2.18±0.38 mL/min), and that of C group was obviously higher versus controls (P < 0.05). After 5 weeks of intragastric intervention by Glurenorm, the body mass of the mice in control and C group was evidently lower relative to A group, and that of C group was obviously higher versus controls (P < 0.05). Mice in control and C group were remarkably lower in body mass at the 7th week after Glurenorm intervention versus A group, and C group was relatively lower versus controls (P < 0.05). In short, EMT played an important role in promoting the occurrence and progression of renal fibrosis. Glurenorm can reduce the progression of renal fibrosis, inhibit EMT of renal tubular epithelial cells, and effectively protect kidney function.

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Sphingosine kinase 1 protects renal tubular epithelial cells from renal fibrosis via induction of autophagy

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2017.07.011 ◽

2017 ◽

Vol 90 ◽

pp. 17-28 ◽

Cited By ~ 18

Author(s):

Chunyang Du ◽

Yunzhuo Ren ◽

Fang Yao ◽

Jialiang Duan ◽

Hui’er Zhao ◽

...

Keyword(s):

Epithelial Cells ◽

Renal Fibrosis ◽

Sphingosine Kinase ◽

Sphingosine Kinase 1 ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Renal Tubular

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Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis

Open Medicine ◽

10.1515/med-2021-0328 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1336-1349

Author(s):

Qianlan Dong ◽

Qiong Wang ◽

Xiaohui Yan ◽

Xiaoming Wang ◽

Zhenjiang Li ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Epithelial Cells ◽

High Glucose ◽

Quantitative Polymerase Chain Reaction ◽

Cell Counting ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Renal Tubular

Abstract Background Diabetic nephropathy (DN) is a common diabetic complication. Long noncoding RNAs (lncRNAs) have been identified as essential regulators in DN progression. This study is devoted to the research of lncRNA-myocardial infarction-associated transcript (MIAT) in DN. Methods DN cell model was established by high glucose (HG) treatment for human renal tubular epithelial cells (HK-2). Cell viability and colonizing capacity were analyzed by Cell Counting Kit-8 (CCK-8) and colony formation assay. Apoptosis was assessed via caspase-3 detection and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used for evaluating inflammation. The protein determination was completed using western blot. MIAT, microRNA-182-5p (miR-182-5p), and G protein-coupled receptor class C group 5 member A (GPRC5A) levels were all examined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Intergenic binding was verified using dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. Results HG induced the inhibition of cell growth, but accelerated apoptosis and inflammation as well as the activation of nuclear factor kappa B (NF-κB) pathway. MIAT reestablishment prevented the HG-induced cell damages and NF-κB signal activation. Mechanistically, MIAT was proved as a miR-182-5p sponge and regulated the expression of GPRC5A that was a miR-182-5p target. The rescued experiments demonstrated that MIAT downregulation or miR-182-5p upregulation aggravated the HG-induced cell damages and activated the NF-κB pathway via the respective regulation of miR-182-5p or GPRC5A. Conclusion Taken together, MIAT functioned as an inhibitory factor in the pathogenesis to impede the development of DN and inactivate the NF-κB pathway via regulating the miR-182-5p/GPRC5A axis.

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