Epigenetic modulation of immune cells: Mechanisms and implications

Advances in Biological Regulation, Journal Year: 2024, Volume and Issue: 94, P. 101043 - 101043

Published: Aug. 10, 2024

Language: Английский

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CircHIPK3 Alleviates High Glucose Toxicity to Human Renal Tubular Epithelial HK-2 Cells Through Regulation of miR-326/miR-487a-3p/SIRT1

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2021, Volume and Issue: Volume 14, P. 729 - 740

Published: Feb. 1, 2021

The intervention of circular RNA HIPK3 (circHIPK3) in diabetes has drawn increasing attention recent years. However, the underlying mechanism circHIPK3 diabetic nephropathy (DN) not been fully elucidated. Thus, current study aims to investigate role high glucose (HG)-induced toxicity human renal tubular epithelial HK-2 cells.The expression cells induced by HG was determined qRT-PCR and Western blot. regulatory effects miR-326/miR-487a-3p on proliferative apoptosis were evaluated CCK-8 flow cytometry. Dual-luciferase reporter assay applied predict target genes miR-326 or miR-487a-3p.Expression level remarkably decreased after treatment HG. overexpression effectively reversed HG-induced cell proliferation inhibition apoptosis. Furthermore, SIRT1 confirmed be gene miR-487a-3p, which showed downstream circHIPK3. silencing miR-487a-3p also proved induce reduce cells.Our data suggest that can attenuate inhibit through sponging regulate SIRT1.

Language: Английский

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Interactions among Long Non-Coding RNAs and microRNAs Influence Disease Phenotype in Diabetes and Diabetic Kidney Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 6027 - 6027

Published: June 2, 2021

Large-scale RNA sequencing and genome-wide profiling data revealed the identification of a heterogeneous group noncoding RNAs, known as long RNAs (lncRNAs). These lncRNAs play central roles in health disease processes diabetes cancer. The critical association between aberrant expression diabetic kidney have been reported. LncRNAs regulate diverse targets can function sponges for regulatory microRNAs, which influence phenotype kidneys. Importantly, microRNAs may bidirectional or crosstalk mechanisms, need to be further investigated. studies offer novel possibility that used potential therapeutic diseases. Here, we discuss functions mechanisms actions lncRNAs, their interactions with provide insight promise targets, emphasizing role pathogenesis disease.

Language: Английский

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Circular RNAs; powerful microRNA sponges to overcome diabetic nephropathy

Pathology - Research and Practice, Journal Year: 2021, Volume and Issue: 227, P. 153618 - 153618

Published: Sept. 15, 2021

Language: Английский

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Knockdown of circ_0003928 ameliorates high glucose-induced dysfunction of human tubular epithelial cells through the miR-506-3p/HDAC4 pathway in diabetic nephropathy

European journal of medical research, Journal Year: 2022, Volume and Issue: 27(1)

Published: April 7, 2022

Abstract Background Previous data have indicated the importance of circular RNA (circRNA) in pathogenesis diabetic nephropathy (DN). The study is designed to investigate effects circ_0003928 on oxidative stress and apoptosis high glucose (HG)-treated human tubular epithelial cells (HK-2) underlying mechanism. Methods DN cell model was established by inducing HK-2 using 30 mmol/L D-glucose. expression circ_0003928, miR-506-3p histone deacetylase 4 (HDAC4) detected quantitative real-time polymerase chain reaction. Cell viability proliferation were investigated counting kit-8 5-Ethynyl-29-deoxyuridine (EdU) assays, respectively. Oxidative evaluated commercial kits. Caspase 3 activity apoptotic rate assessed a caspase assay flow cytometry analysis, Protein Western blotting analysis. interactions among HDAC4 identified dual-luciferase reporter pull-down assays. Results Circ_0003928 significantly upregulated, while downregulated serum patients HG-induced cells. HG treatment inhibited proliferation, but induced apoptosis; however, these reversed after depletion. acted as sponge, target gene miR-506-3p. Moreover, circ_0003928/miR-506-3p/HDAC4 axis regulated dysfunction. Conclusion sponge for regulate through HDAC4, which suggested that might be helpful therapy DN.

Language: Английский

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The application value of multimodal ultrasound imaging technology in the prediction of early-stage type 2 diabetic kidney disease

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 11, 2025

Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. This study examines diagnostic efficacy multi-modal ultrasound imaging technology for early detection DKD, offering a valuable reference prompt diagnosis affected patients. The clinical data 88 patients with early-stage type 2 diabetic (E-T2DKD group), 82 uncomplicated diabetes (T2DM and healthy individuals (control group) who underwent physical examinations at outpatient clinic Affiliated Jiangning Hospital Nanjing Medical University, were analyzed. Multimodal (MUIT) was employed to detect various parameter indicators, prediction model developed using receiver operating characteristic (ROC) curve. results indicated no significant differences in age, gender, BMI among three patient groups. In comparison T2DM group, those E-T2DKD group exhibited significantly higher durations HbA1C levels. Significant observed function-related indicators assessed across groups, including Cystatin C, β2-microglobulin (β2-MG), serum retinol-binding protein (S-RBP), creatinine (Scr), plasma urea nitrogen (PUN), estimated glomerular filtration rate (eGFR), urine neutrophil gelatinase-associated lipocalin (U-NGAL), (U-RBP), N-acetyl-β-D-glucosaminidase (U-NAG) urinary albumin excretion rates (UAER) (p < 0.05), whereas found eGFR, Scr PUN levels between control group. Notable statistical groups also identified MUIT parameters, cortex shear wave elastography (SWE), volume index (KVI), interlobar artery (IA) Vsmax, IA Vdmin, resistance (RI), pulsatility (PI) 0.05). SWE, KVI, RI, PI than both while RCT/RMT, Vdmin lower These incorporated into binary logistic regression model, joint predictive value fitted based on coefficients. Further ROC analysis revealed that area under curve (AUC) characteristics reached 0.993, indicating high E-T2DKD.

Language: Английский

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Immunological and Comparative Study of Serum HSP-70 Level and MicroRNA-21 Expression with Clinical Findings in Patients with Diabetic Nephropathy

Al-Kufa University Journal for Biology, Journal Year: 2025, Volume and Issue: 17(1), P. 92 - 98

Published: April 13, 2025

Diabetic nephropathy is an important cause of morbidity and mortality in all types diabetes. MicroRNA-21 expression can be induced by hypoxic conditions such as kidney injury regulated diseases may used a diagnostic biomarker diseases. On the other hand, most people with nephropathy, heat shock protein (HSP 70) has been investigated from different aspects experimental studies. HSP-70 abundant form HSP cells. involved response to various acute chronic well urinary tract infections. The purpose this study compare immunological comparative serum level clinical findings diabetic patients.

Language: Английский

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miR-188-3p abolishes germacrone-mediated podocyte protection in a mouse model of diabetic nephropathy in type I diabetes through triggering mitochondrial injury

Bioengineered, Journal Year: 2021, Volume and Issue: 13(1), P. 774 - 788

Published: Dec. 1, 2021

Mitochondrial injury-triggered podocyte apoptosis is a major risk factor for diabetic nephropathy (DN). However, the detailed relationship between mitochondrial homeostasis and remains unclear. The present study aimed to explore role functional mechanism of germacrone in DN type I diabetes (type DN). A mouse model was established by injecting streptozocin, injury constructed using high glucose (HG) induction. Histopathology detected hematoxylin eosin periodic acid-Schiff staining. Transmission electron microscopy flow cytometry were used evaluate function. Germacrone simultaneously reduced blood glucose, 24 h proteinuria, other nephrotic symptoms 1 model. Moreover, protected against damage, limited reactive oxygen species (ROS) accumulation, restored glutathione peroxidase (GPX) activity GPX4 protein expression, subsequently preventing apoptosis. Mechanistically, increased miR-188-3p expression mice reversed germacrone-challenged mice. HG induced antagonist abolished HG-mediated increase ROS. Notably, found have therapeutic effect aggravating damage alleviates progression limiting apoptosis, which partly counteracted upregulation. combination antagonists expected be an effective strategy DN.

Language: Английский

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MicroRNA-122-5p ameliorates tubular injury in diabetic nephropathy via FIH-1/HIF-1α pathway

Renal Failure, Journal Year: 2022, Volume and Issue: 44(1), P. 293 - 303

Published: Feb. 15, 2022

Diabetes kidney disease (DKD) affects approximately one-third of diabetes patients, however, the specific molecular mechanism DKD remains unclear, and there is still a lack effective therapies. Here, we demonstrated significant increase microRNA-122-5p (miR-122-5p) in renal tubular cells STZ induced diabetic nephropathy (DN) mice. Moreover, inhibition miR-122-5p led to increased cell death serve injury promoted DN progression following treatment mice, whereas supplementation mimic had protective effects this model. In addition, suppressed expression factor inhibiting hypoxia-inducible factor-1 (FIH-1) vitro models DN. microRNA target reporter assay further verified FIH-1 as direct miR-122-5p. Generally, inhibits activity HIF-1α. Our study indicated that overexpression HIF-1α by transfection plasmid reduced death, suggesting role Collectively, these findings may unveil novel miR-122-5p/FIH-1/HIF-1α pathway which can attenuate progression.

Language: Английский

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2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione isolated from Averrhoa carambola L. root inhibits high glucose-induced EMT in HK-2 cells through targeting the regulation of miR-21–5p/Smad7 signaling pathway

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116280 - 116280

Published: Feb. 17, 2024

2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione (DMDD) isolated from Averrhoa carambola L. root, has been proven therapeutic effects on diabetic kidney disease (DKD). This research aims to assess DMDD's DKD and investigate its underlying mechanisms, establish DMDD as a novel pharmaceutical agent for treatment. The human renal tubular epithelial (HK-2) cells were induced by high glucose (HG) mimic followed cytotoxicity of was assessed using the Cell Counting Kit-8 (CCK-8) assay. migratory capacity HK-2 evaluated through transwell scratch-wound assays. To effect Smad7 miR-21–5p, lentiviral transfection employed in cells. Additionally, expression proteins related epithelial-mesenchymal transition (EMT) TGFβ1/Smad2/3 pathway checked QRT-PCR, Western blot, immunofluorescence techniques. study shown that significantly suppresses cell migration Vimentin, α-SMA, TGFβ1, p-Smad2/3 under HG conditions. Concurrently, enhances protein E-cadherin Smad7. Intriguingly, abrogated upon silencing. Further investigations revealed effectively inhibits miR-21–5p expression, which is upregulated HG. Downregulation activation EMT In contrast, overexpression negates benefits. mitigates HG-induced modulating miR-21–5p/Smad7 pathway, thereby inhibiting fibrosis DKD. These findings suggest holds promise potential

Language: Английский

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