scholarly journals MicroRNAs in Diabetic Kidney Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Rong Li ◽  
Arthur C. K. Chung ◽  
Xueqing Yu ◽  
Hui Y. Lan
Keyword(s):  
Kidney Disease ◽  
Messenger Rna ◽  
Diabetic Kidney Disease ◽  
Target Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Diagnostic Tools ◽  
Diabetic Kidney ◽  
Functional Studies ◽  
Gene Expression Studies

Rapid growth of diabetes and diabetic kidney disease exerts a great burden on society. Owing to the lack of effective treatments for diabetic kidney disease, treatment relies on drugs that either reduces its progression or involve renal replacement therapies, such as dialysis and kidney transplantation. It is urgent to search for biomarkers for early diagnosis and effective therapy. The discovery of microRNAs had lead to a new era of post-transcriptional regulators of gene expression. Studies from cells, experimental animal models and patients under diabetic conditions demonstrate that expression patterns of microRNAs are altered during the progression of diabetic kidney disease. Functional studies indicate that the ability of microRNAs to bind 3′ untranslated region of messenger RNA not only shows their capability to regulate expression of target genes, but also their therapeutic potential to diabetic kidney disease. The presence of microRNAs in plasma, serum, and urine has been shown to be possible biomarkers in diabetic kidney disease. Therefore, identification of the pathogenic role of microRNAs possesses an important clinical impact in terms of prevention and treatment of progression in diabetic kidney disease because it allows us to design novel and specific therapies and diagnostic tools for diabetic kidney disease.

scholarly journals MicroRNAs: new biomarkers and promising therapeutic targets for diabetic kidney disease

2019 ◽  
Vol 41 (3) ◽  
pp. 412-422 ◽  
Author(s):  
Linicene Rosa do Nascimento ◽  
Caroline Pereira Domingueti
Keyword(s):  
Kidney Disease ◽  
Messenger Rna ◽  
Diabetic Kidney Disease ◽  
Regulation Of Gene Expression ◽  
Therapeutic Targets ◽  
Diabetic Kidney ◽  
Rna Molecules ◽  
Global Health Issue ◽  
New Biomarkers ◽  
Post Transcriptional Regulation

Abstract Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus associated with significant morbidity and mortality regarded as a global health issue. MicroRNAs - small RNA molecules responsible for the post-transcriptional regulation of gene expression by degradation of messenger RNA or translational repression of protein synthesis - rank among the factors linked to the development and progression of DKD. This study aimed to offer a narrative review on investigations around the use of microRNAs in the diagnosis, monitoring, and treatment of DKD. Various microRNAs are involved in the pathogenesis of DKD, while others have a role in nephroprotection and thus serve as promising therapeutic targets for DKD. Serum and urine microRNAs levels have also been considered in the early diagnosis and monitoring of individuals with DKD, since increases in albuminuria, decreases in the glomerular filtration rate, and progression of DKD have been linked to changes in the levels of some microRNAs.

scholarly journals Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential

2017 ◽  
Vol 75 (4) ◽  
pp. 669-688 ◽  
Author(s):  
Danyi Yang ◽  
Man J. Livingston ◽  
Zhiwen Liu ◽  
Guie Dong ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Therapeutic Potential ◽  
Diabetic Kidney

scholarly journals Adiponectin level in diabetic kidney disease the relationship with glycemic control and microvascular complications; a mystery unresolved

2018 ◽  
Vol 6 (1) ◽  
pp. 18
Author(s):  
Effat A. E. Tony ◽  
Mohamed H.Mostafa ◽  
Refaat F. Abdelaal ◽  
Abeer A. Tony ◽  
Tahra El- Shereif ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Therapeutic Potential ◽  
Microvascular Complications ◽  
Multivariate Logistic Regression Analysis ◽  
Vascular Complications ◽  
Predictive Biomarkers ◽  
Therapeutic Interventions ◽  
Diabetic Patients ◽  
Diabetic Kidney

Background: Defining new predictive biomarkers in diabetic kidney disease (DKD) would provide a window of opportunity for preventive and/or therapeutic interventions to prevent or delay the onset of irreversible long-term micro and or macro vascular complications. Adiponectin (ADPN) has been variously associated with diabetic microvascular complications; however, no comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications.Aim of study: we aimed to measure the plasma levels of adiponectin in patients with type 2 diabetes mellitus, to assess whether these levels vary with the different stages of DKD according to their e GFR and to evaluate its relation to their microvascular complications and glycemic control.Methods: This is a prospective observational study including 100 T2DM classified into two groups according to their albuminuria levels and estimated GFR. Participants subjected to thorough history taking and clinical examination. Serum level of ADPN was assessed in all patients.Results: Serum ADPN levels were significantly lower in T2DM patients with nephropathy (P = 0.001), while their levels were non-significantly higher in patients with non-proliferative retinopathy or neuropathy. Their levels were lowered with more advanced stages of DKD with nephropathy and the decrement was dependent on their severity (P<0.001). Levels of ADPN with cutoff value of < 22600 (μg/mL) had ability to diagnose microvascular complications in our diabetic patients with sensitivity (81%) and specificity (27%). Multivariate logistic regression analysis showed that the odds ratio for the presence of nephropathy in the lowest tertile of ADPN was 1.09 (95% CI; 11.45- 13.08, P= 0.06), therefore, ADPN was not an independent risk factor for diabetic nephropathy. However, its higher level was independently associated with increased odds for the presence of neuropathy in particular. Conclusions: ADPN plays a role in the pathogenesis of microvasculopathy in diabetic patients and help to identify high-risk patients and modulate the therapeutic potential in the prevention of DKD.  

scholarly journals Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity

2021 ◽  
Vol 22 (4) ◽  
pp. 1546
Author(s):  
Christian Sávio-Silva ◽  
Poliana E. Soinski-Sousa ◽  
Antônio Simplício-Filho ◽  
Rosana M. C. Bastos ◽  
Stephany Beyerstedt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Diabetic Kidney ◽  
Ros Accumulation

Diabetic kidney disease (DKD) is a worldwide microvascular complication of type 2 diabetes mellitus (T2DM). From several pathological mechanisms involved in T2DM-DKD, we focused on mitochondria damage induced by hyperglycemia-driven reactive species oxygen (ROS) accumulation and verified whether mesenchymal stem cells (MSCs) anti-oxidative, anti-apoptotic, autophagy modulation, and pro-mitochondria homeostasis therapeutic potential curtailed T2DM-DKD progression. For that purpose, we grew immortalized glomerular mesangial cells (GMCs) in hyper glucose media containing hydrogen peroxide. MSCs prevented these cells from apoptosis-induced cell death, ROS accumulation, and mitochondria membrane potential impairment. Additionally, MSCs recovered GMCs’ biogenesis and mitophagy-related gene expression that were downregulated by stress media. In BTBRob/ob mice, a robust model of T2DM-DKD and obesity, MSC therapy (1 × 106 cells, two doses 4-weeks apart, intra-peritoneal route) led to functional and structural kidney improvement in a time-dependent manner. Therefore, MSC-treated animals exhibited lower levels of urinary albumin-to-creatinine ratio, less mesangial expansion, higher number of podocytes, up-regulation of mitochondria-related survival genes, a decrease in autophagy hyper-activation, and a potential decrease in cleaved-caspase 3 expression. Collectively, these novel findings have important implications for the advancement of cell therapy and provide insights into cellular and molecular mechanisms of MSC-based therapy in T2DM-DKD setting.

scholarly journals FcER1: A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Swastika Sur ◽  
Mark Nguyen ◽  
Patrick Boada ◽  
Tara K. Sigdel ◽  
Hans Sollinger ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Target Genes ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Rational Drug Design ◽  
Transcriptional Analysis ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p &lt; 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p &lt; 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.

scholarly journals Therapeutic Targeting of SGLT2: A New Era in the Treatment of Diabetes and Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
James Shaffner ◽  
Bohan Chen ◽  
Deepak K. Malhotra ◽  
Lance D. Dworkin ◽  
Rujun Gong
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Therapeutic Potential ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Metabolic Reprogramming ◽  
Therapeutic Modality ◽  
Future Research ◽  
Bodyweight Loss ◽  
Diabetic Kidney

As the prevalence of diabetic kidney disease (DKD) continues to rise, so does the need for a novel therapeutic modality that can control and slow its progression to end-stage renal disease. The advent of sodium-glucose cotransporter-2 (SGLT2) inhibitors has provided a major advancement for the treatment of DKD. However, there still remains insufficient understanding of the mechanism of action and effectiveness of this drug, and as a result, its use has been very limited. Burgeoning evidence suggests that the SGLT2 inhibitors possess renal protective activities that are able to lower glycemic levels, improve blood pressure/hemodynamics, cause bodyweight loss, mitigate oxidative stress, exert anti-inflammatory and anti-fibrotic effects, reduce urinary albumin excretion, lower uric acid levels, diminish the activity of intrarenal renin-angiotensin-aldosterone system, and reduce natriuretic peptide levels. SGLT2 inhibitors have been shown to be safe and beneficial for use in patients with a GFR ≥30mL/min/1.73m2, associated with a constellation of signs of metabolic reprogramming, including enhanced ketogenesis, which may be responsible for the correction of metabolic reprogramming that underlies DKD. This article aims to provide a comprehensive overview and better understanding of the SGLT2 inhibitor and its benefits as it pertains to renal pathophysiology. It summarizes our recent understanding on the mechanisms of action of SGLT2 inhibitors, discusses the effects of SGLT2 inhibitors on diabetes and DKD, and presents future research directions and therapeutic potential.

scholarly journals Identification of Key Candidate Genes and Chemical Perturbagens in Diabetic Kidney Disease Using Integrated Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuo Gao ◽  
Aishwarya S ◽  
Xiao-mei Li ◽  
Xin-lun Li ◽  
Li-na Sui
Keyword(s):  
Gene Expression ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Kinase Inhibitor ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Patients ◽  
Diabetic Kidney

Globally, nearly 40 percent of all diabetic patients develop serious diabetic kidney disease (DKD). The identification of the potential early-stage biomarkers and elucidation of their underlying molecular mechanisms in DKD are required. In this study, we performed integrated bioinformatics analysis on the expression profiles GSE111154, GSE30528 and GSE30529 associated with early diabetic nephropathy (EDN), glomerular DKD (GDKD) and tubular DKD (TDKD), respectively. A total of 1,241, 318 and 280 differentially expressed genes (DEGs) were identified for GSE30258, GSE30529, and GSE111154 respectively. Subsequently, 280 upregulated and 27 downregulated DEGs shared between the three GSE datasets were identified. Further analysis of the gene expression levels conducted on the hub genes revealed SPARC (Secreted Protein Acidic And Cysteine Rich), POSTN (periostin), LUM (Lumican), KNG1 (Kininogen 1), FN1 (Fibronectin 1), VCAN (Versican) and PTPRO (Protein Tyrosine Phosphatase Receptor Type O) having potential roles in DKD progression. FN1, LUM and VCAN were identified as upregulated genes for GDKD whereas the downregulation of PTPRO was associated with all three diseases. Both POSTN and SPARC were identified as the overexpressed putative biomarkers whereas KNG1 was found as downregulated in TDKD. Additionally, we also identified two drugs, namely pidorubicine, a topoisomerase inhibitor (LINCS ID- BRD-K04548931) and Polo-like kinase inhibitor (LINCS ID- BRD-K41652870) having the validated role in reversing the differential gene expression patterns observed in the three GSE datasets used. Collectively, this study aids in the understanding of the molecular drivers, critical genes and pathways that underlie DKD initiation and progression.

scholarly journals Midkine, a heparin-binding protein, is increased in the diabetic mouse kidney postmenopause

2011 ◽  
Vol 300 (1) ◽  
pp. F139-F146 ◽  
Author(s):  
Maggie K. Diamond-Stanic ◽  
Melissa J. Romero-Aleshire ◽  
Patricia B. Hoyer ◽  
Kevin Greer ◽  
James B. Hoying ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Dna Microarrays ◽  
Diabetic Kidney Disease ◽  
Target Genes ◽  
Histidine Decarboxylase ◽  
Early Response ◽  
Diabetic Mouse ◽  
Kidney Cortex ◽  
Heparin Binding ◽  
Diabetic Kidney

Estrogen is thought to protect against the development of chronic kidney disease, and menopause increases the development and severity of diabetic kidney disease. In this study, we used streptozotocin (STZ) to induce diabetes in the 4-vinylcyclohexene diepoxide (VCD)-treated mouse model of menopause. DNA microarrays were used to identify gene expression changes in the diabetic kidney postmenopause. An ANOVA model, CARMA, was used to isolate the menopause effect between two groups of diabetic mice, diabetic menopausal (STZ/VCD) and diabetic cycling (STZ). In this diabetic study, 8,864 genes of the possible 15,600 genes on the array were included in the ANOVA; 99 genes were identified as demonstrating a >1.5-fold up- or downregulation between the STZ/VCD and STZ groups. We randomly selected genes for confirmation by real-time PCR; midkine (Mdk), immediate early response gene 3 (IEX-1), mitogen-inducible gene 6 (Mig6), and ubiquitin-specific protease 2 (USP2) were significantly increased in the kidneys of STZ/VCD compared with STZ mice. Western blot analysis confirmed that Mdk and IEX-1 protein abundance was significantly increased in the kidney cortex of STZ/VCD compared with STZ mice. In a separate study, DNA microarrays and CARMA analysis were used to identify the effect of menopause on the nondiabetic kidney; VCD-treated mice were compared with cycling mice. Of the possible 15,600 genes on the array, 9,142 genes were included in the ANOVA; 20 genes were identified as demonstrating a >1.5-fold up- or downregulation; histidine decarboxylase and vanin 1 were among the genes identified as differentially expressed in the postmenopausal nondiabetic kidney. These data expand our understanding of how hormone status correlates with the development of diabetic kidney disease and identify several target genes for further studies.

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