scholarly journals Adiponectin and Its Receptors in Diabetic Kidney Disease: Molecular Mechanisms and Clinical Potential

Endocrinology ◽  
2017 ◽  
Vol 158 (7) ◽  
pp. 2022-2034 ◽  
Author(s):  
Dongqing Zha ◽  
Xiaoyan Wu ◽  
Ping Gao
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Diabetic Kidney ◽  
Clinical Potential

scholarly journals Exercise Ameliorates Diabetic Kidney Disease in Type 2 Diabetic Fatty Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1754
Author(s):  
Itaru Monno ◽  
Yoshio Ogura ◽  
Jing Xu ◽  
Daisuke Koya ◽  
Munehiro Kitada
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Male Rats ◽  
Fatty Acid Binding ◽  
Diabetic Kidney ◽  
Beneficial Effects ◽  
Type 2 Diabetic

Lifestyle improvement, including through exercise, has been recognized as an important mode of therapy for the suppression of diabetic kidney disease (DKD). However, the detailed molecular mechanisms by which exercise exerts beneficial effects in the suppression of DKD have not yet been fully elucidated. In this study, we investigate the effects of treadmill exercise training (TET) for 8 weeks (13 m/min, 30 min/day, 5 days/week) on kidney injuries of type 2 diabetic male rats with obesity (Wistar fatty (fa/fa) rats: WFRs) at 36 weeks of age. TET significantly suppressed the levels of albuminuria and urinary liver-type fatty-acid-binding protein (L-FABP), tubulointerstitial fibrosis, inflammation, and oxidative stress in the kidneys of WFRs. In addition, TET mitigated excessive apoptosis and restored autophagy in the renal cortex, as well as suppressed the development of morphological abnormalities in the mitochondria of proximal tubular cells, which were also accompanied by the restoration of AMP-activated kinase (AMPK) activity and suppression of the mechanistic target of rapamycin complex 1 (mTORC1). In conclusion, TET ameliorates diabetes-induced kidney injury in type 2 diabetic fatty rats.

scholarly journals Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease

2020 ◽  
Vol 21 (11) ◽  
pp. 4113
Author(s):  
Julio M. Martinez-Moreno ◽  
Miguel Fontecha-Barriuso ◽  
Diego Martin-Sanchez ◽  
Juan Guerrero-Mauvecin ◽  
Elena Goma-Garces ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Epigenetic Regulation ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Sglt2 Inhibitors ◽  
Post Translational Modifications ◽  
Diabetic Kidney ◽  
Bet Inhibitor

Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications—histone methylation, acetylation and crotonylation—in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of β-hydroxybutyrate, a molecule that generates a specific histone modification, β-hydroxybutyrylation, which has been associated with the beneficial health effects of fasting. To what extent this impact on epigenetic regulation may underlie or contribute to the so-far unclear molecular mechanisms of cardio- and nephroprotection offered by SGLT2 inhibitors merits further in-depth studies.

scholarly journals Multi-scalar data integration links glomerular angiopoietin-tie signaling pathway activation with progression of diabetic kidney disease

2021 ◽  
Author(s):  
Jiahao Liu ◽  
Viji Nair ◽  
Yi-yang Zhao ◽  
Dong-yuan Chang ◽  
Felix Eichinger ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Receptor Expression ◽  
Diabetic Kidney ◽  
Scalar Data ◽  
Chinese Cohort ◽  
End Stage ◽  
Angiopoietin 2

Diabetes is the leading cause of chronic kidney disease. Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of diabetic kidney disease (DKD). In the Clinical Phenotyping and Resource Biobank study, an unbiased, machine learning approach identified a three-marker panel from plasma proteomics which, when added to standard clinical parameters, improved the prediction of outcome of end-stage kidney disease (ESKD) or 40% decline in baseline glomerular filtration rate (GFR) in a discovery DKD group (N=58) and was validated in an independent group (N=68) who also had kidney transcriptomic profiles available. Of the three markers, plasma angiopoietin 2 (ANGPT2) remained significantly associated with composite outcome in 210 Chinese Cohort Study of Chronic Kidney Disease participants with DKD. The glomerular transcriptional Angiopoietin/Tie (ANG-TIE) activation scores, derived from the expression of 154 literature-curated ANG-TIE signaling mediators, positively correlated with plasma ANGPT2 levels and outcome, explained by substantially higher TEK receptor expression in glomeruli and higher ANG-TIE activation scores in endothelial cells in DKD by single cell RNA sequencing. Our work suggests that activation of glomerular ANG-TIE signaling in the kidneys underlies the association of plasma ANGPT2 with disease progression, thereby providing potential targets to prevent DKD progression.

scholarly journals Molecular mechanisms of diabetic kidney disease

2014 ◽  
Vol 124 (6) ◽  
pp. 2333-2340 ◽  
Author(s):  
Kimberly Reidy ◽  
Hyun Mi Kang ◽  
Thomas Hostetter ◽  
Katalin Susztak
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Diabetic Kidney

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 A Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of Shuilu Erxian Dan in Treating Diabetic Kidney Disease

2020 ◽  
Author(s):  
Tingchao Wu ◽  
Rensong Yue ◽  
Mingmin He
Keyword(s):  
Kidney Disease ◽  
Signaling Pathway ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Experimental Studies ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Active Components ◽  
Diabetic Kidney

Abstract Background and objective: Recent years, some Chinese scholars have applied Shuilu Erxian Dan (SED) to the treatment of treating diabetic kidney disease (DKD) and achieved well curative effect. However, these studies are mostly limited to clinical observation. This study aimed to explore the molecular mechanisms of SED in treating DKD. Methods The active components of SED were retrieved in TCMSP database and BATMAN-TCM database, and the herbal targets were obtained by drugbank database and SwissTargetPrediction platform. The gene expression data of DKD patients were downloaded from GEO database and analyzed to obtain DKD-related targets. The ingredient-target network and the PPI network were constructed by Cytoscape software. The clusterProfiler package of R software is used for bioinformatic analysis. Molecular docking was further applied to verify the interaction between compounds and targets by Autodock Vina software. Results 610 differential expressed genes of DKD patients were obtained, and 29 potential targets of SED against DKD were screened out (including PPTGS2, FABP3, HSD17B2, FABP1, HSD11B2, CYP27B1, JUN, UGT2B7, VCAM1, CA2, MAOA, MMP2, CXCR1, SLC22A6, EPHX2, SLC47A1, FOS, EGF, CCL2, COL3A1, GSTA1, GSTA2, HSPA1A, DAO, ALDH2, ALB, GPR18, FPR2, and LPL). All the active ingredients in SED can act on the DKD-related targets, among which quercetin, Ellagic acid, and kaempferol may be the key active compounds. SED may play a therapeutic role in DKD by regulating pathways including “Fluid shear stress and atherosclerosis”, “AGE − RAGE signaling pathway in diabetic complications” and “IL-17 signaling pathway”. Conclusion This study suggests that the mechanism of SED treating DKD is a complex network with multi-target and multi-pathway, which provides a reference for future experimental studies.

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 Molecular Mechanisms in Early Diabetic Kidney Disease: Glomerular Endothelial Cell Dysfunction

2020 ◽  
Vol 21 (24) ◽  
pp. 9456
Author(s):  
Emelie Lassén ◽  
Ilse S. Daehn
Keyword(s):  
Endothelial Cell ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Early Stage ◽  
Endothelial Cell Dysfunction ◽  
Glomerular Endothelial Cell ◽  
Diabetic Kidney ◽  
Cell Dysfunction

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), with prevalence increasing at an alarming rate worldwide and today, there are no known cures. The pathogenesis of DKD is complex, influenced by genetics and the environment. However, the underlying molecular mechanisms that contribute to DKD risk in about one-third of diabetics are still poorly understood. The early stage of DKD is characterized by glomerular hyperfiltration, hypertrophy, podocyte injury and depletion. Recent evidence of glomerular endothelial cell injury at the early stage of DKD has been suggested to be critical in the pathological process and has highlighted the importance of glomerular intercellular crosstalk. A potential mechanism may include reactive oxygen species (ROS), which play a direct role in diabetes and its complications. In this review, we discuss different cellular sources of ROS in diabetes and a new emerging paradigm of endothelial cell dysfunction as a key event in the pathogenesis of DKD.

scholarly journals General Control of Amino Acid Synthesis 5-Like 1-Mediated Acetylation of Manganese Superoxide Dismutase Regulates Oxidative Stress in Diabetic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Tingting Lv ◽  
Yao Lu ◽  
Yi Liu ◽  
Hong Feng ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Renal Injury ◽  
Manganese Superoxide Dismutase ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Acid Synthesis ◽  
Amino Acid Synthesis ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD). In the past few decades, there has been a large amount of evidence to highlight the pivotal role of oxidative stress in the development and progression of DKD. However, the detailed molecular mechanisms are not fully elucidated. A new sight has been established that the mitochondrial acetyltransferase GCN5L1 participates in cellular redox homeostasis maintenance in DKD. Firstly, we found that the expression of GCN5L1 is significantly elevated both in human and mouse kidney tissues with DKD and in hyperglycemic renal tubular epithelial cells (TECs), while deletion of GCN5L1 could effectively ameliorate oxidative stress-induced renal injury in DKD. Furthermore, deletion of GCN5L1 could reduce MnSOD acetylation on lysine 68 and activate its activity, thereby scavenging excessive ROS and relieving oxidative stress-induced renal inflammation and fibrosis. In general, GCN5L1-mediated acetylation of MnSOD exacerbated oxidative stress-induced renal injury, suggesting that GCN5L1 might be a potential intervention target in DKD.

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