488-P: Isoliquiritigenin Protects Renal Tubular Epithelial Cells from Inflammatory and Oxidative Injuries via Directly Activating SIRT1 in Type 1 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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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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235-OR: Sphingosine Kinase 2-Mediated Pyroptosis of Renal Tubular Epithelial Cells Contributes to the Progression of Diabetic Nephropathy

Diabetes ◽

10.2337/db19-235-or ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 235-OR

Author(s):

SISHAN YAN ◽

LANMEI LIANG ◽

WENWEN LIU ◽

WAI WILSON CHEUNG ◽

WEI DING ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Epithelial Cells ◽

Sphingosine Kinase ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Sphingosine Kinase 2 ◽

Renal Tubular

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Calcitriol attenuates renal tubular epithelial cells apoptosis via inhibiting p38MAPK signaling in diabetic nephropathy

Acta Diabetologica ◽

10.1007/s00592-020-01554-0 ◽

2020 ◽

Vol 57 (11) ◽

pp. 1327-1335

Author(s):

Yinfeng Guo ◽

Xiaotong Xie ◽

Yu Zhao ◽

Min Zhou ◽

Ying Yang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Epithelial Cells ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

P38mapk Signaling ◽

Renal Tubular

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Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy

Scientific Reports ◽

10.1038/s41598-021-95827-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fengzhen Wang ◽

Haihan Sun ◽

Bangjie Zuo ◽

Kun Shi ◽

Xin Zhang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Epithelial Cells ◽

Early Stage ◽

Tubulointerstitial Fibrosis ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Sprague Dawley ◽

Mesenchymal Transition ◽

Renal Tubulointerstitial Fibrosis ◽

Renal Tubular

AbstractThis study aimed at comparing the effects of metformin on tubulointerstitial fibrosis (TIF) in different stages of diabetic nephropathy (DN) in vivo and evaluating the mechanism in high glucose (HG)-treated renal tubular epithelial cells (RTECs) in vitro. Sprague–Dawley (SD) rats were used to establish a model of DN, and the changes of biochemical indicators and body weight were measured. The degree of renal fibrosis was quantified using histological analysis, immunohistochemistry, and immunoblot. The underlying relationship between autophagy and DN, and the cellular regulatory mechanism of metformin on epithelial-to-mesenchymal transition (EMT) were investigated. Metformin markedly improved renal function and histological restoration of renal tissues, especially in the early stages of DN, with a significant increase in autophagy and a decrease in the expression of fibrotic biomarkers (fibronectin and collagen I) in renal tissue. Under hyperglycemic conditions, renal tubular epithelial cells inactivated p-AMPK and activated partial EMT. Metformin-induced AMPK significantly ameliorated renal autophagic function, inhibited the partial EMT of RTECs, and attenuated TIF, all of which effectively prevented or delayed the onset of DN. This evidence provides theoretical and experimental basis for the following research on the potential clinical application of metformin in the treatment of diabetic TIF.

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Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/8708236 ◽

2020 ◽

Vol 2020 ◽

pp. 1-22 ◽

Cited By ~ 3

Author(s):

Xue Jiang ◽

Xue-lei Ruan ◽

Yi-xue Xue ◽

Shuang Yang ◽

Mai Shi ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Epithelial Cells ◽

Rna Binding ◽

Positive Staining ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Stat3 Pathway ◽

New Ideas ◽

Renal Tubular ◽

Low Expression

Senescence of renal tubular epithelial cells plays an important role in diabetic nephropathy, but the mechanism is unknown. Metformin may alleviate diabetic nephropathy by reducing this senescence. This study is aimed at clarifying the effects and mechanism of metformin on the senescence of renal tubular epithelial cells in diabetic nephropathy. We found that metformin reduced the expression of senescence-associated gene P21 in high-glucose-induced (30 mmol/L) renal tubular epithelial cells and decreased the β-galactosidase positive staining rate (decreased 16%, p<0.01). Metformin was able to reduce senescence by upregulating the expression of RNA-binding protein MBNL1 and miR-130a-3p and reducing STAT3 expression. MBNL1 prolonged the half-life of miR-130a-3p, and miR-130a-3p could negatively regulate STAT3 by binding to its mRNA 3′UTR. In db/db diabetic mice, we found an enhanced senescence level combined with low expression of MBNL1 and miR-130a-3p and high expression of STAT3 compared with db/m control mice during nephropathy development. Meanwhile, metformin (200 mg/kg/day) could increase the expression of MBNL1 and miR-130a-3p and decreased STAT3 expression, thus reducing this senescence in db/db mice. Our results suggest that metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway, which provided new ideas for the therapy of this disease.

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