scholarly journals Role of Nutrient-Sensing Signals in the Pathogenesis of Diabetic Nephropathy

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Shinji Kume ◽  
Daisuke Koya ◽  
Takashi Uzu ◽  
Hiroshi Maegawa
Keyword(s):  
Diabetic Nephropathy ◽  
Therapeutic Potential ◽  
Nutrient Sensing ◽  
Tubular Cells ◽  
New Findings ◽  
Proximal Tubular ◽  
Stage Renal Disease ◽  
End Stage ◽  
Autophagy Activity

Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. The multipronged drug approach still fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to improve the prognosis of diabetic nephropathy is urgently required. Nutrient-sensing signals and their related intracellular machinery have evolved to combat prolonged periods of starvation in mammals; and these systems are conserved in the kidney. Recent studies have suggested that the activity of three nutrient-sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney. Furthermore, autophagy activity, which is regulated by the above-mentioned nutrient-sensing signals, is also altered in both podocytes and proximal tubular cells under diabetic conditions. Under diabetic conditions, an altered nutritional state owing to nutrient excess may disturb cellular homeostasis regulated by nutrient-responsible systems, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing relationships between nutrient-sensing signals, autophagy, and diabetic nephropathy and suggest the therapeutic potential of nutrient-sensing signals in diabetic nephropathy.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Kosuke Yamahara ◽  
Mako Yasuda ◽  
Shinji Kume ◽  
Daisuke Koya ◽  
Hiroshi Maegawa ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mammalian Cells ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Serum Levels ◽  
New Findings ◽  
Proximal Tubular ◽  
Stage Renal Disease ◽  
End Stage ◽  
Autophagy Activity

Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The multipronged drug approach targeting blood pressure and serum levels of glucose, insulin, and lipids fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to combat diabetic nephropathy is required. Autophagy is a catabolic process that degrades damaged proteins and organelles in mammalian cells and plays a critical role in maintaining cellular homeostasis. The accumulation of proteins and organelles damaged by hyperglycemia and other diabetes-related metabolic changes is highly associated with the development of diabetic nephropathy. Recent studies have suggested that autophagy activity is altered in both podocytes and proximal tubular cells under diabetic conditions. Autophagy activity is regulated by both nutrient state and intracellular stresses. Under diabetic conditions, an altered nutritional state due to nutrient excess may interfere with the autophagic response stimulated by intracellular stresses, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing the relationships between autophagy and diabetic nephropathy and suggest the therapeutic potential of autophagy in diabetic nephropathy.

scholarly journals The Role of Non-coding RNAs in Diabetic Nephropathy-Related Oxidative Stress

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyun He ◽  
Gaoyan Kuang ◽  
Yi Zuo ◽  
Shuangxi Li ◽  
Suxian Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Interstitial Fibrosis ◽  
Rna Molecules ◽  
Non Coding Rnas ◽  
Molecular Therapeutic ◽  
Stage Renal Disease ◽  
End Stage ◽  
Molecular Therapeutic Targets

Diabetic nephropathy (DN) is one of the main complications of diabetes and the main cause of diabetic end-stage renal disease, which is often fatal. DN is usually characterized by progressive renal interstitial fibrosis, which is closely related to the excessive accumulation of extracellular matrix and oxidative stress. Non-coding RNAs (ncRNAs) are RNA molecules expressed in eukaryotic cells that are not translated into proteins. They are widely involved in the regulation of biological processes, such as, chromatin remodeling, transcription, post-transcriptional modification, and signal transduction. Recent studies have shown that ncRNAs play an important role in the occurrence and development of DN and participate in the regulation of oxidative stress in DN. This review clarifies the functions and mechanisms of ncRNAs in DN-related oxidative stress, providing valuable insights into the prevention, early diagnosis, and molecular therapeutic targets of DN.

scholarly journals The Role of MicroRNAs in Diabetic Nephropathy

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Hao Wu ◽  
Lili Kong ◽  
Shanshan Zhou ◽  
Wenpeng Cui ◽  
Feng Xu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Critical Role ◽  
Good Prospect ◽  
Protective Effects ◽  
Protein Coding ◽  
Diagnostic Strategies ◽  
Pathogenic Factors ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN), as one of the chronic complications of diabetes, is the major cause of end-stage renal disease. However, the pathogenesis of this disease is not fully understood. In recent years, research on microRNAs (miRNAs) has become a hotspot because of their critical role in regulating posttranscriptional levels of protein-coding genes that may serve as key pathogenic factors in diseases. Several miRNAs were found to participate in the pathogenesis of DN, while others showed renal protective effects. Therefore, targeting miRNAs that are involved in DN may have a good prospect in the treatment of the disease. The aim of this review is to summarize DN-related miRNAs and provide potential targets for diagnostic strategies and therapeutic intervention.

scholarly journals The Role of Chemokines and Chemokine Receptors in Diabetic Nephropathy

2020 ◽  
Vol 21 (9) ◽  
pp. 3172 ◽  
Author(s):  
Ting-Ting Chang ◽  
Jaw-Wen Chen
Keyword(s):  
Diabetic Nephropathy ◽  
End Stage Renal Disease ◽  
Chemokine Receptors ◽  
Potential Role ◽  
Chronic Inflammatory Disease ◽  
Direct Effects ◽  
Stage Renal Disease ◽  
End Stage ◽  
Kidney Function Decline

Kidney function decline is one of the complications of diabetes mellitus and may be indicated as diabetic nephropathy (DN). DN is a chronic inflammatory disease featuring proteinuria and a decreasing glomerular filtration rate. Despite several therapeutic options being currently available, DN is still the major cause of end-stage renal disease. Accordingly, widespread innovation is needed to improve outcomes in patients with DN. Chemokines and their receptors are critically involved in the inflammatory progression in the development of DN. Although recent studies have shown multiple pathways related to the chemokine system, the specific and direct effects of chemokines and their receptors remain unclear. In this review, we provide an overview of the potential role and mechanism of chemokine systems in DN proposed in recent years. Chemokine system-related mechanisms may provide potential therapeutic targets in DN.

scholarly journals Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

2020 ◽  
Vol 21 (8) ◽  
pp. 2806 ◽  
Author(s):  
Priscila Calle ◽  
Georgina Hotter
Keyword(s):  
Diabetic Nephropathy ◽  
Interstitial Fibrosis ◽  
Vascular Dysfunction ◽  
Inflammatory Cells ◽  
Macrophage Phenotype ◽  
Progressive Decline ◽  
Potential Factors ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in 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 C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Liwen Zhang ◽  
Fangfang Zhou ◽  
Xialian Yu ◽  
Yufei Zhu ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Biological Process ◽  
Critical Role ◽  
Kidney Injury ◽  
The Elderly ◽  
Chronological Aging ◽  
Tubular Cells ◽  
Complex Biological Process ◽  
Stage Renal Disease ◽  
End Stage

Abstract Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of C/EBPα in podocyte senescence and kidney aging by generating a genetically modified mouse model of chronological aging in which C/EBPα was selectively deleted in podocytes and by overexpressing C/EBPα in cultured podocytes, in which premature senescence was induced by treatment with adriamycin. Moreover, we illuminated the mechanisms by which podocyte senescence causes tubular impairment by stimulating HK-2 cells with bovine serum albumin (BSA) and chloroquine. Our findings suggest that C/EBPα knockout in podocytes aggravates podocyte senescence through the AMPK/mTOR pathway, leading to glomerulosclerosis, and that subsequent albuminuria exacerbates the epithelial–mesenchymal transdifferentiation of senescent tubular cells by suppressing autophagy. These observations highlight the importance of C/EBPα as a new potential target in kidney aging.

scholarly journals Role of Endothelial Nitric Oxide Synthase in Diabetic Nephropathy: Lessons from Diabetic eNOS Knockout Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Takamune Takahashi ◽  
Raymond C. Harris
Keyword(s):  
Animal Model ◽  
Diabetic Nephropathy ◽  
Critical Role ◽  
Therapeutic Interventions ◽  
Diabetic Mice ◽  
Model Study ◽  
Animal Model Study ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in many countries. The animal models that recapitulate human DN undoubtedly facilitate our understanding of this disease and promote the development of new diagnostic markers and therapeutic interventions. Based on the clinical evidence showing the association of eNOS dysfunction with advanced DN, we and others have created diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic mice exhibit advanced nephropathic changes with distinct features of progressive DN, including pronounced albuminuria, nodular glomerulosclerosis, mesangiolysis, and arteriolar hyalinosis. These studies clearly defined a critical role of eNOS in DN and developed a robust animal model of this disease, which enables us to study the pathogenic mechanisms of progressive DN. Further, recent studies with this animal model have explored the novel mechanisms by which eNOS deficiency causes advanced DN and provided many new insights into the pathogenesis of DN. Therefore, here we summarize the findings obtained with this animal model and discuss the roles of eNOS in DN, unresolved issues, and future investigations of this animal model study.

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