scholarly journals The Dynamics and Plasticity of Epigenetics in Diabetic Kidney Disease: Therapeutic Applications Vis-à-Vis

2022 ◽  
Vol 23 (2) ◽  
pp. 843
Author(s):  
Feng-Chih Kuo ◽  
Chia-Ter Chao ◽  
Shih-Hua Lin
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Cell Types ◽  
Electrolyte Imbalance ◽  
Metabolic Disturbances ◽  
Diabetic Kidney ◽  
Epigenetic Biomarkers

Chronic kidney disease (CKD) refers to the phenomenon of progressive decline in the glomerular filtration rate accompanied by adverse consequences, including fluid retention, electrolyte imbalance, and an increased cardiovascular risk compared to those with normal renal function. The triggers for the irreversible renal function deterioration are multifactorial, and diabetes mellitus serves as a major contributor to the development of CKD, namely diabetic kidney disease (DKD). Recently, epigenetic dysregulation emerged as a pivotal player steering the progression of DKD, partly resulting from hyperglycemia-associated metabolic disturbances, rising oxidative stress, and/or uncontrolled inflammation. In this review, we describe the major epigenetic molecular mechanisms, followed by summarizing current understandings of the epigenetic alterations pertaining to DKD. We highlight the epigenetic regulatory processes involved in several crucial renal cell types: Mesangial cells, podocytes, tubular epithelia, and glomerular endothelial cells. Finally, we highlight epigenetic biomarkers and related therapeutic candidates that hold promising potential for the early detection of DKD and the amelioration of its progression.

scholarly journals miR-379 deletion ameliorates features of diabetic kidney disease by enhancing adaptive mitophagy via FIS1

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mitsuo Kato ◽  
Maryam Abdollahi ◽  
Ragadeepthi Tunduguru ◽  
Walter Tsark ◽  
Zhuo Chen ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Mesangial Cells ◽  
Mitochondrial Fission ◽  
Major Complication ◽  
Body Weight Loss ◽  
Diabetic Kidney ◽  
Guide Rna ◽  
And Oxidative Stress

AbstractDiabetic kidney disease (DKD) is a major complication of diabetes. Expression of members of the microRNA (miRNA) miR-379 cluster is increased in DKD. miR-379, the most upstream 5′-miRNA in the cluster, functions in endoplasmic reticulum (ER) stress by targeting EDEM3. However, the in vivo functions of miR-379 remain unclear. We created miR-379 knockout (KO) mice using CRISPR-Cas9 nickase and dual guide RNA technique and characterized their phenotype in diabetes. We screened for miR-379 targets in renal mesangial cells from WT vs. miR-379KO mice using AGO2-immunopreciptation and CLASH (cross-linking, ligation, sequencing hybrids) and identified the redox protein thioredoxin and mitochondrial fission-1 protein. miR-379KO mice were protected from features of DKD as well as body weight loss associated with mitochondrial dysfunction, ER- and oxidative stress. These results reveal a role for miR-379 in DKD and metabolic processes via reducing adaptive mitophagy. Strategies targeting miR-379 could offer therapeutic options for DKD.

scholarly journals Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease: The PREDIAN Trial

2014 ◽  
Vol 26 (1) ◽  
pp. 220-229 ◽  
Author(s):  
Juan F. Navarro-González ◽  
Carmen Mora-Fernández ◽  
Mercedes Muros de Fuentes ◽  
Jesús Chahin ◽  
María L. Méndez ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Urinary Albumin Excretion ◽  
Urinary Albumin ◽  
Diabetic Kidney ◽  
Albumin Excretion

scholarly journals BKCa Mediates Dysfunction in High Glucose Induced Mesangial Cell Injury via TGF-β1/Smad2/3 Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Zhigui Wu ◽  
Wenxian Yin ◽  
Mengqi Sun ◽  
Yuankai Si ◽  
Xiaoxiao Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kidney Disease ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Diabetic Kidney

Objective. To explore the role and mechanism of BKCa in diabetic kidney disease. Methods. Rat mesangial cells (MCs) HBZY-1 were cultured with high glucose to simulate the high-glucose environment of diabetic kidney disease in vivo. The effects of large conductance calcium-activated potassium channel (BKCa) on proliferation, migration, and apoptosis of HBZY-1 cells were observed. The contents of transforming growth factor beta 1 (TGF-β1), Smad2/3, collagen IV (Col IV), and fibronectin (FN) in the extracellular matrix were also observed. Results. High glucose significantly damaged HBZY-1 cells, which enhanced the ability of cell proliferation, migration, and apoptosis, and increased the secretion of Col IV and FN. Inhibition of BKCa and TGF-β1/Smad2/3 signaling pathways can inhibit the proliferation, migration, and apoptosis of HBZY-1 cells and suppress the secretion of Col IV and FN. The effect of excitation is the opposite. Conclusions. BKCa regulates mesangial cell proliferation, migration, apoptosis, and secretion of Col IV and FN and is associated with TGF-β1/Smad2/3 signaling pathway.

scholarly journals SO004IDENTIFICATION OF HUB GENES, FOCUSED ON CHEMOKINES AND CHEMOKINE RECEPTORS, ASSOCIATED WITH THE DECLINE OF RENAL FUCTION OF DIABETIC KIDNEY DISEASE BY WEIGHTED GENE CO-EXPRESSION NETWORK ANALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Songtao Feng ◽  
Bicheng Liu ◽  
Linli Lv ◽  
Gao Yueming ◽  
Di Yin ◽  
...  
Keyword(s):  
Renal Function ◽  
Network Analysis ◽  
Kidney Disease ◽  
T Cell Activation ◽  
Chemokine Receptors ◽  
Diabetic Kidney Disease ◽  
Expression Level ◽  
Hub Genes ◽  
Diabetic Kidney ◽  
Gene Modules

Abstract Background and Aims The fact that activation of the innate immune system and chronic inflammation are closely involved in the pathogenesis of diabetic Kidney disease (DKD). Recent studies have suggested the inflammatory process plays a crucial role in the progression of DKD. Identifying novel inflammatory molecules closely related to the decline of renal function is of significance in diagnosing and predicting the progression of DKD. The weighted gene co-expression network analysis (WGCNA) algorithm represents a novel systems biology method that provide the approach of association between gene modules and clinical traits to find the genes involvement into the certain phenotypic trait. The goal of this study was to identify hub genes and their roles in DKD from the gene sets associated with the decline of renal function by WGCNA. Method The Gene Expression Omnibus (GEO) database and “Nephroseq” website were searched and transcriptome study from DN biopsies with well-established clinical phenotypic data were selected for analysis. Next, we constructed a weighted gene co-expression network and identified modules negatively correlated with eGFR by WGCNA in the data of glomerular tissue. Functional annotations of the genes in modules negatively correlated with eGFR were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Through protein-protein interaction (PPI) analysis and hub gene screening, the hub genes were obtained. Furthermore, we compared the expression level of hub genes between DKD and normal control and drew ROC curves to determine the diagnosis value to DKD of these genes. Results The microarray-based expression datasets GSE30528 were screened out for analysis, which included glomeruli tissue of 9 cases of DKD and 13 cases of control. This microarray platform represented the transcriptome profile of 12411 well-characterized genes. Using WGCNA, a total of 19 gene modules were identified. Then module eigengene were analyzed for correlation with clinical traits of age, sex, ethnicity and eGFR and the “MEhoneydew1” module showed negative associated with eGFR (r=-0.58). GO functional annotation showed that these 551 genes in the “MEhoneydew1” module mainly enriched in the T cell activation. KEGG annotation showed mainly enriched in chemokine signaling pathway. Except for C3, top 10 hub genes, CCR5, CXCR4, CCR7, CCL5, CXCL8, CCR2, CCR1, CX3CR1, C3AR1 and C3, are all members of chemokines or chemokine receptors. Furthermore, we compared the expression level of these 9 genes between DKD and control, and found that all of these 9 genes increased in the DKD group, and the differences of 6 genes, CCR5, CCR7, CCL5, CCR2, CCR1, C3AR1, were of statistical significance. Linear correlation analysis showed that the expression of these 6 genes was negatively correlated with eGFR, and the ROC curve showed that the area under the curve could reach 0.812∼1.0. Conclusion We identified a panel of 6 hub genes focused on chemokines and chemokine receptors critical for decline of renal function of DKD using WGCNA. These genes may serve as biomarkers for diagnosis/prognosis and as putative novel therapeutic targets for DKD.

scholarly journals Suppressed ER‐associated degradation by intraglomerular cross talk between mesangial cells and podocytes causes podocyte injury in diabetic kidney disease

2020 ◽  
Vol 34 (11) ◽  
pp. 15577-15590
Author(s):  
Daisuke Fujimoto ◽  
Takashige Kuwabara ◽  
Yusuke Hata ◽  
Shuro Umemoto ◽  
Tomoko Kanki ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Cross Talk ◽  
Diabetic Kidney Disease ◽  
Mesangial Cells ◽  
Podocyte Injury ◽  
Diabetic Kidney

scholarly journals Glomerular endothelial cell injury and cross talk in diabetic kidney disease

2015 ◽  
Vol 308 (4) ◽  
pp. F287-F297 ◽  
Author(s):  
Jia Fu ◽  
Kyung Lee ◽  
Peter Y. Chuang ◽  
Zhihong Liu ◽  
John Cijiang He
Keyword(s):  
Endothelial Cell ◽  
Kidney Disease ◽  
Cross Talk ◽  
Diabetic Kidney Disease ◽  
Cell Injury ◽  
Mesangial Cells ◽  
Glomerular Endothelial Cell ◽  
Glomerular Cell ◽  
Diabetic Kidney ◽  
Endothelial Cell Surface

Diabetic kidney disease (DKD) remains a leading cause of new-onset end-stage renal disease (ESRD), and yet, at present, the treatment is still very limited. A better understanding of the pathogenesis of DKD is therefore necessary to develop more effective therapies. Increasing evidence suggests that glomerular endothelial cell (GEC) injury plays a major role in the development and progression of DKD. Alteration of the glomerular endothelial cell surface layer, including its major component, glycocalyx, is a leading cause of microalbuminuria observed in early DKD. Many studies suggest a presence of cross talk between glomerular cells, such as between GEC and mesangial cells or GEC and podocytes. PDGFB/PDGFRβ is a major mediator for GEC and mesangial cell cross talk, while vascular endothelial growth factor (VEGF), angiopoietins, and endothelin-1 are the major mediators for GEC and podocyte communication. In DKD, GEC injury may lead to podocyte damage, while podocyte loss further exacerbates GEC injury, forming a vicious cycle. Therefore, GEC injury may predispose to albuminuria in diabetes either directly or indirectly by communication with neighboring podocytes and mesangial cells via secreted mediators. Identification of novel mediators of glomerular cell cross talk, such as microRNAs, will lead to a better understanding of the pathogenesis of DKD. Targeting these mediators may be a novel approach to develop more effective therapy for DKD.

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 Prevalence of and risk factors for chronic kidney disease and diabetic kidney disease in a central Chinese urban population: a cross-sectional survey

2019 ◽  
Author(s):  
Jiayu Duan ◽  
Duan Guang-Cai ◽  
Wang Chong-Jian ◽  
Liu Dong-Wei ◽  
Qiao Ying-Jin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Logistic Regression ◽  
Renal Function ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Density Lipoprotein ◽  
Ordinal Logistic Regression ◽  
Central China ◽  
Diabetic Kidney

Abstract Background This study was conducted to evaluate and update the current prevalence of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a China. Methods A total of 5231 participants were randomly recruited for this study. CKD and DKD were defined according to the combination of estimated glomerular filtration rate (eGFR), presence of albuminuria and diabetes. Participants completed a questionnaire assessing lifestyle and relevant medical history, and blood and urinary specimens were taken. Serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and urinary albumin were assessed. The age- and gender-adjusted prevalences of CKD and DKD were calculated, and risk factors associated with the presence of reduced eGFR, albuminuria, DKD, severity of albuminuria and progression of reduce renal function were analyzed by binary and ordinal logistic regression. Results The overall adjusted prevalence of CKD was 16.8% (15.8 – 17.8%) and that of DKD was 3.5% (3.0 – 4.0%). Decreased renal function was detected in 132 participants [2.9%, 95% confidence interval (CI): 2.5 – 3.2%], whereas albuminuria was found in 858 participants (14.9%, 95% CI: 13.9 – 15.9%). In all participants with diabetes, the prevalence of reduced eGFR was 6.3% (95% CI = 3.9 – 8.6%) and that of albuminuria was 45.3% (95% CI = 40.4 – 50.1%). The overall prevalence of CKD in participants with diabetes was 48.0% (95% CI = 43.1 – 52.9%). The results of the binary and ordinal logistic regression indicated that factors independently associated with higher risk of reduced eGFR and albuminuria were older age, gender, smoking, alcohol consumption, overweight, obesity, diabetes, hypertension, dyslipidemia and hyperuricemia. Conclusions Our study shows the current prevalences of CKD and DKD in residents of Central China. The high prevalence suggests an urgent need to implement interventions to relieve the high burden of CKD and DKD in China.

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