Circ-ACTR2 aggravates the high glucose-induced cell dysfunction of human renal mesangial cells through mediating the miR-205-5p/HMGA2 axis in diabetic nephropathy

Abstract Background Circular RNAs (circRNAs) have been considered as pivotal biomarkers in Diabetic nephropathy (DN). CircRNA ARP2 actin-related protein 2 homolog (circ-ACTR2) could promote the HG-induced cell injury in DN. However, how circ-ACTR2 acts in DN is still unclear. This study aimed to explore the molecular mechanism of circ-ACTR2 in DN progression, intending to provide support for the diagnostic and therapeutic potentials of circ-ACTR2 in DN. Methods RNA expression analysis was conducted by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell growth was measured via Cell Counting Kit-8 and EdU assays. Inflammatory response was assessed by Enzyme-linked immunosorbent assay. The protein detection was performed via western blot. Oxidative stress was evaluated by the commercial kits. The molecular interaction was affirmed through dual-luciferase reporter and RNA immunoprecipitation assays. Results Circ-ACTR2 level was upregulated in DN samples and high glucose (HG)-treated human renal mesangial cells (HRMCs). Silencing the circ-ACTR2 expression partly abolished the HG-induced cell proliferation, inflammation and extracellular matrix accumulation and oxidative stress in HRMCs. Circ-ACTR2 was confirmed as a sponge for miR-205-5p. Circ-ACTR2 regulated the effects of HG on HRMCs by targeting miR-205-5p. MiR-205-5p directly targeted high-mobility group AT-hook 2 (HMGA2), and HMGA2 downregulation also protected against cell injury in HG-treated HRMCs. HG-mediated cell dysfunction was repressed by miR-205-5p/HMGA2 axis. Moreover, circ-ACTR2 increased the expression of HMGA2 through the sponge effect on miR-205-5p in HG-treated HRMCs. Conclusion All data have manifested that circ-ACTR2 contributed to the HG-induced DN progression in HRMCs by the mediation of miR-205-5p/HMGA2 axis.

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Hyperoside Alleviates High Glucose-Induced Proliferation of Mesangial Cells through the Inhibition of the ERK/CREB/miRNA-34a Signaling Pathway

International Journal of Endocrinology ◽

10.1155/2020/1361924 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Le Zhang ◽

Qian Dai ◽

Lanlan Hu ◽

Hua Yu ◽

Jing Qiu ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

High Glucose ◽

Mesangial Cells ◽

Viable Cell ◽

Underlying Mechanism ◽

Cell Counting ◽

Luciferase Reporter ◽

Dependent Manner ◽

Glomerular Mesangial Cells

Purpose. Hyperoside, a flavonoid isolated from conventional medicinal herbs, has been demonstrated to exert a significant protective effect in diabetic nephropathy. This study aimed to determine the underlying mechanisms, by which hyperoside inhibits high glucose-(HG-) induced proliferation in mouse renal mesangial cells. Methods. Mouse glomerular mesangial cells line (SV40-MES13) was used to study the inhibitory effect of hyperoside on cell proliferation induced by 30 mM glucose, which was used to simulate a diabetic condition. Viable cell count was assessed using the Cell Counting Kit-8 and by the 5-ethynyl-20-deoxyuridine incorporation assay. The underlying mechanism involving miRNA-34a was further investigated by quantitative RT-PCR and transfection with miRNA-34a agomir. The phosphorylation levels of extracellular signal-regulated kinases (ERKs) and cAMP-response element-binding protein (CREB) were measured by Western blotting. The binding region and the critical binding sites of CREB in the miRNA-34a promoter were investigated by the chromatin immunoprecipitation assay and luciferase reporter assay, respectively. Results. We found that hyperoside could significantly decrease HG-induced proliferation of SV40-MES13 cells in a dose-dependent manner, without causing obvious cell death. In addition, hyperoside inhibited the activation of ERK pathway and phosphorylation of its downstream transcriptional factor CREB, as well as the miRNA-34a expression. We further confirmed that CREB-mediated regulation of miRNA-34a is dependent on the direct binding to specific sites in the promoter region of miRNA-34a. Conclusion. Our cumulative results suggested that hyperoside inhibits the proliferation of SV40-MES13 cells through the suppression of the ERK/CREB/miRNA-34a signaling pathway, which provides new insight to the current investigation on therapeutic strategies for diabetic nephropathy.

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Circ_0000491 Promotes Apoptosis, Inflammation, Oxidative Stress, and Fibrosis in High Glucose-Induced Mesangial Cells by Regulating miR-455-3p/Hmgb1 Axis

Nephron ◽

10.1159/000516870 ◽

2021 ◽

pp. 1-12

Author(s):

Jing Wang ◽

Shifeng Yang ◽

Wendong Li ◽

Ming Zhao ◽

Kai Li

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

High Glucose ◽

Mesangial Cells ◽

Stress Factors ◽

Luciferase Reporter ◽

Circular Rnas ◽

Enzyme Linked Immunosorbent Assay ◽

Induced Apoptosis ◽

Related Proteins

Background: Diabetic nephropathy (DN) is a severe microvascular complication of diabetes. Recently, many circular RNAs can exert crucial roles in DN progression. This study intended to explore the role and mechanism of circ_0000491 in DN. Methods: The DN mouse model was constructed by streptozotocin injection, and the DN cell model was established using high glucose (HG) treatment in mouse mesangial cells (SV40-MES13). The expression of circ_0000491 and microRNA-455-3p (miR-455-3p) was detected by quantitative real-time polymerase chain reaction. Cell apoptosis was evaluated by flow cytometry. The expression levels of high-mobility group box 1 (Hmgb1) protein, apoptosis-related proteins, and fibrosis-related proteins were examined by the Western blot assay. The release of inflammatory cytokines was assessed by enzyme-linked immunosorbent assay. The oxidative stress factors were analyzed by corresponding kits. The predicted interaction between miR-455-3p and circ_0000491 or Hmgb1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: Circ_0000491 was overexpressed in the DN mouse model and HG-induced SV40-MES13 cells. Knockdown of circ_0000491 weakened HG-induced apoptosis, inflammation, oxidative stress, and fibrosis in SV40-MES13 cells. miR-455-3p was a direct target of circ_0000491, and miR-455-3p inhibition could reverse the role of circ_0000491 silencing in HG-induced SV40-MES13 cells. Moreover, Hmgb1 was a target gene of miR-455-3p, and miR-455-3p played a protective role against HG-induced cell injury by targeting Hmgb1. In addition, circ_0000491 regulated Hmgb1 expression by sponging miR-455-3p. Conclusion: Circ_0000491 knockdown inhibited HG-induced apoptosis, inflammation, oxidative stress, and fibrosis in SV40-MES13 cells by regulating miR-455-3p/Hmgb1 axis.

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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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Knockdown of circ-FANCA alleviates LPS-induced HK2 cell injury via targeting miR-93-5p/OXSR1 axis in septic acute kidney injury

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00625-8 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Heyun Li ◽

Xia Zhang ◽

Peng Wang ◽

Xiaoyan Zhou ◽

Haiying Liang ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Cell Injury ◽

Kidney Injury ◽

Cell Counting ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Septic Acute Kidney Injury ◽

Hk2 Cells ◽

And Oxidative Stress

Abstract Background Sepsis is life-threatening disease with systemic inflammation and can lead to various diseases, including septic acute kidney injury (AKI). Recently, diverse circular RNAs (circRNAs) are considered to be involved in the development of this disease. In this study, we aimed to elucidate the role of circ-FANCA and the potential action mechanism in sepsis-induced AKI. Methods HK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. The expression of circ-FANCA, microRNA-93-5p (miR-93-5p) and oxidative stress responsive 1 (OXSR1) mRNA was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Cell apoptosis and cell cycle distribution were measured by flow cytometry. The inflammatory response was monitored according to the release of pro-inflammatory cytokines via enzyme-linked immunosorbent assay (ELISA). The activities of oxidative indicators were examined using the corresponding kits. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the interaction between miR-93-5p and circ-FANCA or OXSR1. Protein analysis was conducted through western blot. Results Circ-FANCA was upregulated in septic AKI serum specimens and LPS-treated HK2 cells. Functionally, circ-FANCA knockdown facilitated cell proliferation and restrained apoptosis, inflammation and oxidative stress in LPS-triggered HK2 cells. Further mechanism analysis revealed that miR-93-5p was a target of circ-FANCA and circ-FANCA modulated LPS-induced cell damage by targeting miR-93-5p. Meanwhile, miR-93-5p overexpression repressed LPS-treated HK2 cell injury by sponging OXSR1. Furthermore, circ-FANCA regulated OXSR1 expression by sponging miR-93-5p. Besides, exosome-derived circ-FANCA was upregulated in LPS-induced HK2 cells, which was downregulated by GW4869. Conclusion Circ-FANCA knockdown attenuated LPS-induced HK2 cell injury by regulating OXSR1 expression via targeting miR-93-5p.

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MiR-10b alleviates high glucose-induced human retinal endothelial cell injury by regulating TIAM1 signaling

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i8.2 ◽

2020 ◽

Vol 19 (8) ◽

pp. 1577-1583

Author(s):

Yaohua Chen ◽

Yanqing Zhu ◽

Sheng Zhao

Keyword(s):

Endothelial Cell ◽

High Glucose ◽

Target Genes ◽

Cell Injury ◽

Cell Counting ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Ros Production ◽

Qrt Pcr ◽

Retinal Endothelial Cell

Purpose: To investigate the effects of microRNA (miR)-10b on high glucose (HG)-induced human retinal endothelial cell (HREC) injury and the mechanisms involved.Methods: Levels of miR-10b were measured in HRECs using quantitative reverse transcriptasepolymerase chain reaction (qRT-PCR) after the addition of glucose (5.5 and 30 mM). Cell viability was measured using Cell Counting Kit-8 assay, while levels of reactive oxygen species (ROS) weredetermined using fluorimetry. An enzyme-linked immunosorbent assay (ELISA) was used to measure cellular apoptosis. Luciferase reporter assay was used to validate the miR-10b-binding sites of target genes. The levels of T-cell lymphoma invasion and metastasis (TIAM1) and NADPH oxidase-2 (NOX2) were determined using qRT-PCR. Ras-related C3 botulinum toxin substrate 1 (Rac1) activation was evaluated using a pull-down assay. The protein levels of TIAM1 and Rac1 were assayed by western blotting.Results: After HG stimulation, miR-10b expression was downregulated. Viability of HRECs decreased, whereas ROS production increased. However, the overexpression of miR-10b inhibited apoptosis and ROS production in HG-treated HRECs (p < 0.05), while luciferase reporter analysis revealed a possible binding site for miR-10b to target the 3'-untranslated region (UTR) of TIAM1. In addition, the overexpression of miR-10b distinctly reduced the expression levels of TIAM1 and NOX2, but decreased the activation of Rac1 in HG-treated HRECs (p < 0.05); these inhibitory effects of miR-10b were significantly reversed after TIAM1 application.Conclusion: MiR-10b alleviates HG-induced HREC injury by regulating TIAM1 signaling. MiR-10b therapy is a potential therapeutic strategy for patients suffering from diabetic retinopathy. Keywords: MicroRNA-10b, Human retinal endothelial cells, High glucose, TIAM1-Rac1 axis

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LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis

BMC Endocrine Disorders ◽

10.1186/s12902-021-00781-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xuan Wang ◽

Yan Liu ◽

Jian Rong ◽

Kai Wang

Keyword(s):

High Glucose ◽

Mesangial Cells ◽

Quantitative Polymerase Chain Reaction ◽

Cell Counting ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Inflammatory Factor ◽

Glomerular Mesangial Cells ◽

Serum Samples ◽

Human Glomerular Mesangial Cells

Abstract Background Long non-coding RNAs (lncRNAs) are widely reported to be involved in the development of human diseases. HLA complex P5 (HCP5) deregulation is associated with various diseases. However, the function of HCP5 in diabetic nephropathy (DN) is unclear. Methods Human glomerular mesangial cells (HGMCs) were treated with high glucose (HG) to establish DN cell models. The expression of HCP5, miR-93-5p and high mobility group AT-hook 2 (HMGA2) mRNA was detected using quantitative polymerase chain reaction (QPCR). Cell proliferation and cell apoptosis were assessed using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of apoptosis- and fibrosis-related proteins and HMGA2 protein was quantified by western blot. The release of pro-inflammatory factor was checked using enzyme-linked immunosorbent assay (ELISA). The predicted relationship between miR-93-5p and HCP5 or HMGA2 was verified using dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay. Results The expression of HCP5 and HMGA2 was enhanced, while the expression of miR-93-5p was declined in DN serum samples and HG-treated HGMCs. HCP5 knockdown or miR-93-5p restoration ameliorated HG-induced HGMC proliferation, fibrosis and inflammation. MiR-93-5p was a target of HCP5, and miR-93-5p inhibition reversed the effects caused by HCP5 knockdown. Moreover, HMGA2 was a target of miR-93-5p, and HMGA2 overexpression abolished the effects of miR-93-5p restoration. HCP5 knockdown inhibited the AKT/mTOR signaling pathway. Conclusion HCP5 was implicated in DN progression by modulating the miR-93-5p/HMGA2 axis, which provided new insights into the understanding of DN pathogenesis.

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Circ-FBXW12 aggravates the development of diabetic nephropathy by binding to miR-31-5p to induce LIN28B

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00757-x ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Aidong Sun ◽

Ningshuang Sun ◽

Xiao Liang ◽

Zhenbo Hou

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Cell Proliferation ◽

Diabetic Nephropathy ◽

Quantitative Polymerase Chain Reaction ◽

Cell Counting ◽

Luciferase Reporter ◽

Circular Rnas ◽

Enzyme Linked Immunosorbent Assay ◽

And Oxidative Stress

Abstract Background The involvement of circular RNAs (circRNAs) in diabetic nephropathy (DN) has been gradually identified. In this study, we aimed to explore the functions of circRNA F-box/WD repeat-containing protein 12 (circ-FBXW12) in DN development. Methods Reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay was performed for the levels of circ-FBXW12, FBXW12 mRNA, microRNA-31-5p (miR-31-5p) and Lin-28 homolog B (LIN28B) mRNA. RNase R assay was used to analyze the stability of circ-FBXW12. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and 5-ethynyl-2′- deoxyuridine (EdU) assay were employed to evaluate cell viability, cell cycle and proliferation, respectively. Enzyme linked immunosorbent assay (ELISA) was done to measure the concentrations of inflammatory cytokines. Western blot assay was conducted for protein levels. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were examined with commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the relationships among circ-FBXW12, miR-31-5p and LIN28B. Results Circ-FBXW12 level was increased in DN patients’ serums and high glucose (HG)-induced human mesangial cells (HMCs). Circ-FBXW12 knockdown suppressed cell proliferation, arrested cell cycle, reduced extracellular matrix (ECM) production and oxidative stress in HG-induced HMCs. Circ-FBXW12 was identified as the sponge for miR-31-5p, which then directly targeted LIN28B. MiR-31-5p inhibition reversed circ-FBXW12 knockdown-mediated effects on cell proliferation, cell cycle process, ECM production and oxidative in HG-triggered HMCs. Moreover, miR-31-5p overexpression showed similar results with circ-FBXW12 knockdown in HG-stimulated HMC progression, while LIN28B elevation reversed the effects. Conclusion Circ-FBXW12 knockdown suppressed HG-induced HMC growth, inflammation, ECM accumulation and oxidative stress by regulating miR-31-5p/LIN28B axis.

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ALK7 Inhibition Protects Osteoblast Cells Against High Glucose-induced ROS Production via Nrf2/HO-1 Signaling Pathway

Current Molecular Medicine ◽

10.2174/1566524021666210614144337 ◽

2021 ◽

Vol 21 ◽

Author(s):

Zhen Zhao ◽

Yu Lu ◽

Huan Wang ◽

Xiang Gu ◽

Luting Zhu ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Signaling Pathway ◽

High Glucose ◽

Collagen I ◽

Cell Counting ◽

Enzyme Linked Immunosorbent Assay ◽

Heme Oxygenase 1 ◽

Ros Production ◽

Alizarin Red

Background: Some studies demonstrated that under high-glucose (HG) condition, osteoblasts develop oxidative stress, which will impair their normal functions. The effects of activin receptor-like kinase 7 (ALK7) silencing on HG-induced osteoblasts remained unclear. Objective: The aim of this study was to explore the effect of ALK7 on HG-induced osteoblasts. Methods: MC3T3-E1 cells were treated with different concentrations of HG (0, 50, 100, 200 and 300mg/dL), and the cell viability was detected using cell counting kit-8 (CCK-8). HG-treated MC3T3-E1 cells were transfected with siALK7 or ALK7 overexpression plasmid or siNrf2, and then the viability and apoptosis were detected by CCK-8 and flow cytometry. The levels of reactive oxygen species (ROS), collagen I and calcification nodule were determined by oxidative stress kits, Enzyme-linked immunosorbent assay and Alizarin red staining. The expressions of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and osteoblast-associated genes were determined by quantitative real-time PCR (qRT-PCR) and Western blot. Results: Cell viability was reduced with HG treatment. Silencing ALK7 inhibited the effect of HG on increasing cell apoptosis and ROS production, reduced cell viability, mineralized nodules, and downregulated collagen I and osteoblast-associated genes expression in MC3T3-E1 cells. ALK7 silencing activated the Nrf2/HO-1 signaling pathway by affecting expressions of HO-1 and Nrf2. ALK7 overexpression had the opposite effects. In addition, siNrf2 partially reversed the effects of ALK7 silencing on HG-induced MC3T3-E1 cells. Conclusion: ALK7 silencing protected osteoblasts under HG condition possibly through activating the Nrf2/HO-1 pathway.

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miR-29a Negatively Affects Glucose-Stimulated Insulin Secretion and MIN6 Cell Proliferation via Cdc42/β-Catenin Signaling

International Journal of Endocrinology ◽

10.1155/2019/5219782 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13

Author(s):

Jing Duan ◽

Xian-Ling Qian ◽

Jun Li ◽

Xing-Hua Xiao ◽

Xiang-Tong Lu ◽

...

Keyword(s):

Cell Proliferation ◽

Insulin Secretion ◽

High Glucose ◽

Cell Counting ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Glucose Stimulation ◽

Inhibition Of Proliferation ◽

Glucose Stimulated Insulin Secretion

Background. Diabetes is a progressive metabolic disease characterized by hyperglycemia. Functional impairment of islet β cells can occur to varying degrees. This impairment can initially be compensated for by proliferation and metabolic changes of β cells. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in β-cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. Methods. Upregulation and downregulation of miR-29a and Cdc42 were accomplished using transient transfection. miR-29a and Cdc42 expression was detected by real-time PCR and western blotting. MIN6 proliferation was detected using a cell counting kit assay. GSIS under high-glucose (20.0 mM) or basal-glucose (5.0 mM) stimulation was detected by enzyme-linked immunosorbent assay. The miR-29a binding site in the Cdc42 mRNA 3′-untranslated region (UTR) was determined using bioinformatics and luciferase reporter assays. Results. miR-29a overexpression inhibited proliferation (P<0.01) and GSIS under high-glucose stimulation (P<0.01). Cdc42 overexpression promoted proliferation (P<0.05) and GSIS under high-glucose stimulation (P<0.05). miR-29a overexpression decreased Cdc42 expression (P<0.01), whereas miR-29a downregulation increased Cdc42 expression (P<0.01). The results showed that the Cdc42 mRNA 3′-UTR is a direct target of miR-29a in vitro. Additionally, Cdc42 reversed miR-29a-mediated inhibition of proliferation and GSIS (P<0.01). Furthermore, miR-29a inhibited β-catenin expression (P<0.01), whereas Cdc42 promoted β-catenin expression (P<0.01). Conclusion. By negatively regulating Cdc42 and the downstream molecule β-catenin, miR-29a inhibits MIN6 proliferation and insulin secretion.

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The Attenuation of Moutan Cortex on Oxidative Stress for Renal Injury in AGEs-Induced Mesangial Cell Dysfunction and Streptozotocin-Induced Diabetic Nephropathy Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/463815 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 28

Author(s):

Minghua Zhang ◽

Liang Feng ◽

Junfei Gu ◽

Liang Ma ◽

Dong Qin ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Transforming Growth Factor Beta ◽

High Glucose ◽

Transforming Growth Factor ◽

Mesangial Cell ◽

Cell Dysfunction ◽

Moutan Cortex

Oxidative stress (OS) has been regarded as one of the major pathogeneses of diabetic nephropathy (DN) through damaging kidney which is associated with renal cells dysfunction. The aim of this study was to investigate whether Moutan Cortex (MC) could protect kidney function against oxidative stressin vitroorin vivo. The compounds in MC extract were analyzed by HPLC-ESI-MS. High-glucose-fat diet and STZ (30 mg kg−1) were used to induce DN rats model, while 200 μg mL−1AGEs were for HBZY-1 mesangial cell damage. The treatment with MC could significantly increase the activity of SOD, glutathione peroxidase (GSH-PX), and catalase (CAT). However, lipid peroxidation malondialdehyde (MDA) was reduced markedlyin vitroorin vivo. Furthermore, MC decreased markedly the levels of blood glucose, serum creatinine, and urine protein in DN rats. Immunohistochemical assay showed that MC downregulated significantly transforming growth factor beta 2 (TGF-β2) protein expression in renal tissue. Our data provided evidence to support this fact that MC attenuated OS in AGEs-induced mesangial cell dysfunction and also in high-glucose-fat diet and STZ-induced DN rats.

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