scholarly journals Diabetic Nephropathy: Novel Molecular Mechanisms and Therapeutic Targets

2020 ◽  
Vol 11 ◽  
Author(s):  
Carlamaria Zoja ◽  
Christodoulos Xinaris ◽  
Daniela Macconi
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Therapeutic Targets ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Experimental Models ◽  
Lipid Lowering ◽  
Diabetic Patients ◽  
Functional Changes

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes mellitus and the leading cause of end-stage kidney disease. The standard treatments for diabetic patients are glucose and blood pressure control, lipid lowering, and renin-angiotensin system blockade; however, these therapeutic approaches can provide only partial renoprotection if started late in the course of the disease. One major limitation in developing efficient therapies for DN is the complex pathobiology of the diabetic kidney, which undergoes a set of profound structural, metabolic and functional changes. Despite these difficulties, experimental models of diabetes have revealed promising therapeutic targets by identifying pathways that modulate key functions of podocytes and glomerular endothelial cells. In this review we will describe recent advances in the field, analyze key molecular pathways that contribute to the pathogenesis of the disease, and discuss how they could be modulated to prevent or reverse DN.

scholarly journals The Role of MicroRNAs in the Pathogenesis of Diabetic Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Jian Tang ◽  
Deyi Yao ◽  
Haiying Yan ◽  
Xing Chen ◽  
Linjia Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Diabetic Patients ◽  
Hemodynamic Changes ◽  
Clinical Value ◽  
New Ideas ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients; it is also an important cause of renal dysfunction, renal fibrosis, and end-stage renal disease. Unfortunately, the pathogenesis of DN is complex and has not yet been fully elucidated; hence, the pathogenesis of DN to determine effective treatments of crucial importance is deeply explored. Early DN research focuses on hemodynamic changes and metabolic disorders, and recent studies have shown the regulatory role of microRNAs (miRNAs) in genes, which may be a new diagnostic marker and therapeutic target for diabetic nephropathy. In this review, we summarize the recent advances in the clinical value and molecular mechanisms of miRNAs in DN, providing new ideas for the diagnosis and treatment of DN.

scholarly journals Advances in Murine Models of Diabetic Nephropathy

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Li-li Kong ◽  
Hao Wu ◽  
Wen-peng Cui ◽  
Wen-hua Zhou ◽  
Ping Luo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Transgenic Animal ◽  
Genetically Engineered ◽  
Diabetic Patients ◽  
Murine Models ◽  
And Gender ◽  
Novel Therapeutic Strategies

Diabetic nephropathy (DN) is one of the microvascular complications of both type 1 and type 2 diabetes, which is also associated with a poor life expectancy of diabetic patients. However, the pathogenesis of DN is still unclear. Thus, it is of great use to establish appropriate animal models of DN for doing research on pathogenesis and developing novel therapeutic strategies. Although a large number of murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic) animal models have been developed, none of them develops renal changes sufficiently reflecting those seen in humans. Here we review the identified murine models of DN from the aspects of genetic background, type of diabetes, method of induction, gene deficiency, animal age and gender, kidney histopathology, and phenotypic alterations in the hope of enhancing our comprehension of genetic susceptibility and molecular mechanisms responsible for this disease and providing new clues as to how to choose appropriate animal models of DN.

Towards Better Drug Repositioning: Targeted Immunoinflammatory Therapy for Diabetic Nephropathy

2019 ◽  
Vol 26 ◽  
Author(s):  
Qin zhang ◽  
Ming Yang ◽  
Ying Xiao ◽  
Yachun Han ◽  
Shikun Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Inflammatory Process ◽  
Drug Repositioning ◽  
Microvascular Complications ◽  
Pathogenic Factor ◽  
Progressive Decline ◽  
Functional Changes ◽  
Sequence Of Events ◽  
Novel Treatment

: Diabetic nephropathy (DN) is one of the most common and important microvascular complications of diabetes mellitus (DM). The main clinical features of DN are proteinuria and a progressive decline in renal function , which are associated with structural and functional changes in the kidney. The pathogenesis of DN is multifactorial, including genetic, metabolic and haemodynamic factors, which can trigger a sequence of events. Controlling metabolic risks such as hyperglycaemia, hypertension and dyslipidaemia is not enough to slow the progression of DN. Recent studies have emphasized immunoinflammation as a critical pathogenic factor in the progression of DN. Therefore, targeting inflammation is considered a potential and novel treatment strategy for DN. In this review, we will briefly introduce the inflammatory process of DN and discuss the anti-inflammatory effects of antidiabetic drugs when treating DN.

scholarly journals Role of Dendritic Cell in Diabetic Nephropathy

2021 ◽  
Vol 22 (14) ◽  
pp. 7554
Author(s):  
Hyunwoo Kim ◽  
Miyeon Kim ◽  
Hwa-Young Lee ◽  
Ho-Young Park ◽  
Hyunjhung Jhun ◽  
...  
Keyword(s):  
T Cells ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Renal Tissue ◽  
Current Treatment ◽  
Diabetic Patients ◽  
Activated T Cells ◽  
Stage Renal Disease ◽  
Incident Cases

Diabetic nephropathy (DN) is one of the most significant microvascular complications in diabetic patients. DN is the leading cause of end-stage renal disease, accounting for approximately 50% of incident cases. The current treatment options, such as optimal control of hyperglycemia and elevated blood pressure, are insufficient to prevent its progression. DN has been considered as a nonimmune, metabolic, or hemodynamic glomerular disease initiated by hyperglycemia. However, recent studies suggest that DN is an inflammatory disease, and immune cells related with innate and adaptive immunity, such as macrophage and T cells, might be involved in its development and progression. Although it has been revealed that kidney dendritic cells (DCs) accumulation in the renal tissue of human and animal models of DN require activated T cells in the kidney disease, little is known about the function of DCs in DN. In this review, we describe kidney DCs and their subsets, and the role in the pathogenesis of DN. We also suggest how to improve the kidney outcomes by modulating kidney DCs optimally in the patients with DN.

STUDY OF PREVALENCE AND CLINICAL PROFILE OF NEPHROPATHY AND RETINOPATHY IN TYPE 2 DIABETES PATIENTS AT TERTIARY CARE CENTER, UDAIPUR

2021 ◽  
pp. 6-8
Author(s):  
Yash Salil Patel
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Tertiary Care ◽  
Positive Family History ◽  
Diabetic Patients

Microvascular complications of Type 2 Diabetes Mellitus (T2DM), (retinopathy and nephropathy) have a similar etiopathogenetic mechanism besides genetic predisposition. Even though these two complications frequently co-exist, their frequency varies. The association of these two signicant complications and their coexistence needs a relook. To study prevalence of retinopathy and nephropathy in Type 2 diabetes mel Aim: litus. Comparison of diabetic retinopathy and nephropathy in Type 2 diabetes mellitus and its correlation of diabetic retinopathy and nephropathy with duration of illness and various risk factors that affects development, progression and severity of diabetic retinopathy and nephropathy. 100 diabetic patients were taken up for study for a period of one year meeti Methodology: ng the criteria for the present study. Detailed history was taken from patient and meticulous examination was done of all patients with special emphasis on renal and ophthalmic symptoms. Clinical data and investigation prole was tabulated. Statistical analysis was done. Among 100 patients, 22 had diabetic retinopathy. Among patients with diab Results & Conclusion: etic retinopathy, 68.18% patients had positive family history. Among 100 patients, 32 had diabetic nephropathy, mean FBS was 207 mg%, PPBS was 317.8 mg% and mean HbA was 9.2%. Among patients with diabetic retinopathy, mean FBS was 211 mg%, PPBS was 324.9 1c mg%, HbA was 9.5%. From this study it is found that diabetic nephropathy starts earlier than retinopathy. In this study 1c hypertension was found to accelerate progression into nephropathy and retinopathy.

COVID-19 and diabetes mellitus: potential metabolic associations

2021 ◽  
Vol 21 ◽  
Author(s):  
Pedro Henrique Abreu da Silva ◽  
Andressa Santos Garcia ◽  
Fábio Aguiar Alves ◽  
André Luis Souza dos Santos ◽  
Cátia Lacerda Sodré
Keyword(s):  
Diabetes Mellitus ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Renin Angiotensin System ◽  
Cell Receptor ◽  
Protective Role ◽  
Infection Process ◽  
Point Of View ◽  
Diabetic Patients ◽  
Viral Binding

: The COVID-19 pandemic turned the SARS-CoV-2 into the main target of scientific research all around the world. Many advances have already been made, but there is still a long way to go to solve the molecular mechanisms related to the process of the SARS-CoV-2 infection, as well as the particularities of the disease, its course and the complex host-pathogen relationships. However, a lot has been theorized and associated with COVID-19, like the worst prognosis of the disease among individuals with some comorbidities, like diabetes mellitus. In this perspective, diabetic patients are repeatedly associated with more severe cases of COVID-19 when compared to non-diabetic patients. Even though ACE2 (angiotensin-converting enzyme 2) was recognized as the host cell receptor for both binding and entering of SARS-CoV-2 particles, it was also pointed out that this enzyme plays an important protective role against pulmonary damage. Therefore, paradoxically as it may seem, the low baseline level of this receptor in people with diabetes is directly linked to a more expressive loss of ACE2 protective effect, which could be one of the possible factors for the worst prognosis of COVID-19. Still, COVID-19 may also have a diabetogenic effect. From this point of view, the main topics that will be highlighted are (i) the mechanism of the viral entry, with special attention to the cellular receptor (ACE2) and the viral binding protein (spike), (ii) the relationship among the renin-angiotensin system, the infection process and the patients' prognosis, (iii) the glucose control and the medicines used in this event, and (iv) a brief analysis on diabetes triggered by COVID-19.

scholarly journals Expression Profiling and Clinical Significance of Plasma MicroRNAs in Diabetic Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jianqin Wang ◽  
Gouqin Wang ◽  
Yaojun Liang ◽  
Xiaochun Zhou
Keyword(s):  
Diabetic Nephropathy ◽  
Clinical Significance ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Clinicopathological Parameters ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Expression Levels ◽  
Plasma Mirnas

Aims. MicroRNAs (miRNAs) stably and abundantly exist in body fluids and have been considered as novel and noninvasive biomarkers for several diseases. The present study is aimed at investigating the expression profiling and clinical significance of plasma miRNAs in the pathogenesis and progression of diabetic nephropathy (DN). Methods. Plasma samples were obtained from 66 DN patients (36 had microalbuminuria and 30 had macroalbuminuria), 36 diabetic patients with normoalbuminuria, and 40 healthy controls. The plasma miRNA profiles were obtained by miRNA low-density array chip and validated by quantitative real-time polymerase chain reaction. The correlations between the differential expression of plasma miRNAs and clinicopathological parameters were explored. Results. miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 were found to be differentially expressed in plasma samples among these three groups: diabetic patients with microalbuminuria, diabetic patients with normoalbuminuria, and healthy controls (P<0.05). The expression levels of miR-150-5p and miR-155-5p in patients with macroalbuminuria were 2.3-fold (P=0.001) and 1.5-fold (P=0.033) higher than patients with microalbuminuria, respectively. However, the expression levels of miR-30e, miR-3196, miR-320, and let-7a-5p were not significantly different between these two groups (P>0.05). Furthermore, plasma miR-150-5p (P=0.016, r = -0.460) and miR-155-5p (P=0.014, r = -0.467) were negatively correlated with the albuminuria excretion rate, while plasma miR-150-5p (P=0.01, r = 0.318) and miR-155-5p (P=0.030, r=0.271) were positively correlated with the estimated glomerular filtration rate. Conclusion. miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 are potentially new diagnostic biomarkers for early DN. miR-150-5p and miR-155-5p may be involved in the pathogenesis and progression of DN. Further research is required to verify these findings and clarify the specific molecular mechanisms.

scholarly journals Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods

2016 ◽  
Vol 37 (5) ◽  
pp. 1181-1188 ◽  
Author(s):  
WAN-NING WANG ◽  
WEN-LONG ZHANG ◽  
GUANG-YU ZHOU ◽  
FU-ZHE MA ◽  
TAO SUN ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Therapeutic Targets

scholarly journals Profile of Diabetic Nephropathy in Southern Morocco

2021 ◽  
Author(s):  
SANAA BENBRIA ◽  
Abdelaali BAHADI ◽  
Youssef ZORKANI ◽  
MOUNIA AZIZI ◽  
yassir zajjari ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Diabetic Nephropathy ◽  
Renin Angiotensin System ◽  
Biological Data ◽  
Diabetic Patients ◽  
Early Management ◽  
Angiotensin System ◽  
Renin Angiotensin

Abstract Diabetic nephropathy (DN) has a steadily increasing prevalence, particularly because of the increase in sedentary lifestyle and obesity. It is defined as the persistent presence of albuminuria in a diabetic patient and requires early management to prevent progression to end-stage renal failure. The purpose of this work is to describe the epidemiologic profile and the progression of DN for the first time in a southern Moroccan region: Guelmim Oued noun - Moroccan Sahara.Patients and methods: It is a retrospective study conducted at the 5th military hospital in Guelmim and including all diabetic patients seen in nephrology consultation between January 2015 and December 2018. We collected the following parameters of our patients: demographics, comorbidities, prescribed treatments and biological data (Albuminuria, renal function and glycated hemoglobin) during their nephrology follow-up.Résults: During the study period 267 diabetic patients were included among 1042 patients, which represented 25.9% of the nephrology consultation activity. Their average age was 64.3 years with a slight male predominance (60%) and only two patients had type 1 diabetes. At the first nephrology consultation the average duration of diabetes was 14.6 years, 61 (22.8%) patients were on diet alone, 95 (35.5%) on oral antidiabetic drugs (OADs), 94 (35.2%) on insulin and 35 (13%) on OAD and insulin. Half the patients were hypertensive and 107 (40%) already had a cardiovascular complication (arterial disease, coronary artery disease or stroke). The average initial albuminuria was 388 mg/24h and the average glomerular filtration rate (GFR) was 67 ml/min ; 115 (43%) patients being in renal failure. 46 (17%) patients had no renal function assessment during their previous follow-up and only 139 (52%) were on renin-angiotensin system inhibitors (RASIs). After 12-month-follow-up in nephrology, the average GFR was 70 ml/min and 64 ml /min after two years.Conclusion: Diabetic nephropathy accounts for at least a quarter of nephrology consultation activity in the region of Guelmim Oued Noun. It is characterized in this context by the delay in treatment using renin angiotensin system inhibitors and late nephrology referral hence the need to strengthen preventive strategies in this region especially continuous training.

scholarly journals Identification of Hub Genes and Potential ceRNA Networks of Diabetic Nephropathy by Weighted Gene Co-Expression Network Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Guoqing Li ◽  
Jun Zhang ◽  
Dechen Liu ◽  
Qiong Wei ◽  
Hui Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Network Analysis ◽  
Disease Progression ◽  
Signaling Pathway ◽  
Microvascular Complications ◽  
Pearson Correlation ◽  
Mapk Signaling ◽  
Diabetic Patients ◽  
Hub Genes ◽  
Regulatory Pathways

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients, and is the main cause of end-stage renal disease. The exact molecular mechanism of DN is not fully understood. The aim of this study was to identify novel biomarkers and mechanisms for DN disease progression by weighted gene co-expression network analysis (WGCNA). From the GSE142153 dataset based on the peripheral blood monouclear cells (PBMC) of DN, we identified 234 genes through WGCNA and differential expression analysis. Gene Ontology (GO) annotations mainly included inflammatory response, leukocyte cell-cell adhesion, and positive regulation of proteolysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways mostly included IL-17 signaling pathway, MAPK signaling pathway, and PPAR signaling pathway in DN. A total of four hub genes (IL6, CXCL8, MMP9 and ATF3) were identified by cytoscape, and the relative expression levels of hub genes were also confirmed by RT-qPCR. ROC curve analysis determined that the expression of the four genes could distinguish DN from controls (the area under the curve is all greater than 0.8), and Pearson correlation coefficient analysis suggested that the expression of the four genes was related to estimated glomerular filtration rate (eGFR) of DN. Finally, through database prediction and literature screening, we constructed lncRNA-miRNA-mRNA network. We propose that NEAT1/XIST/KCNQ1T1-let-7b-5p-IL6, NEAT1/XIST-miR-93-5p-CXCL8 and NEAT1/XIST/KCNQ1T1-miR-27a-3p/miR-16-5p-ATF3 might be potential RNA regulatory pathways to regulate the disease progression of early DN. In conclusion, we identified four hub genes, namely, IL6, CXCL8, MMP9, and ATF3, as markers for early diagnosis of DN, and provided insight into the mechanisms of disease development in DN at the transcriptome level.

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