scholarly journals Nicotine, Smoking, Podocytes and Diabetic Nephropathy

2021 ◽  
Author(s):  
Edgar A. Jaimes ◽  
Ming-Sheng Zhou ◽  
Mohammed Siddiqui ◽  
Gabriel Rezonzew ◽  
Runxia Tian ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Electronic Cigarettes ◽  
Pressure Control ◽  
Lipid Uptake ◽  
Novel Studies ◽  
Filtration Barrier ◽  
Fibronectin Expression ◽  
End Stage ◽  
And Function

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. Besides glycemic and blood pressure control, environmental factors such as cigarette smoking (CS) adversely affect the progression of DN. The effects of CS on DN progression have been attributed to combustion generated molecules without consideration to the role of nicotine (NIC), responsible for the addictive properties of both CS and electronic cigarettes (EC). Podocytes (POD) are essential to preserve the structure and function of the glomerular filtration barrier and strong evidence indicates that early POD loss promotes DN progression. We performed studies in human POD and in a mouse model of diabetes that develops nephropathy resembling human DN. We determined that NIC binding to podocytes in concentrations achieved with CS and EC activated NADPH oxidase, which sets in motion a dysfunctional molecular network integrated by COX2, known to induce podocyte injury; downregulation of AMPK, important for maintaining cellular energy stores and antioxidation and upregulation of CD36 that increased lipid uptake and promoted apoptosis. In diabetic mice NIC increased proteinuria, a recognized marker of CKD progression, accompanied by reduced glomerular podocyte synaptopodin, a crucial stabilizer of POD cytoskeleton and increased fibronectin expression. These novel studies critically implicate NIC itself as a contributor to DN progression in CS and EC users.

scholarly journals Inherited podocytopathies

2008 ◽  
Vol 136 (Suppl. 4) ◽  
pp. 327-339
Author(s):  
Radovan Bogdanovic
Keyword(s):  
Congenital Nephrotic Syndrome ◽  
Structural Studies ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Glomerular Epithelial Cells ◽  
Causes Of Disease ◽  
Stage Renal Disease ◽  
End Stage ◽  
Made In

Podocytes, the visceral glomerular epithelial cells, are the postmythotic cells that line the outer aspects of the glomerular basement membrane. A number of advances have been made in recent years, linked to the discovery of singlegene defects in hereditary glomerular disease, which highlight the role of these cells in preventing proteinuria. Despite the rarity of hereditary proteinuric syndromes, genetic, biochemical, and structural studies of these diseases have made important contributions to our knowledge of how the normal glomerular filter works and the mechanism of proteinuria. The course of these diseases can vary; some patients present with severe proteinuria and congenital nephrotic syndrome, whereas others have only moderate proteinuria and focal segmental glomerulosclerosis. Regardless of its cause, the disease often progresses to end-stage renal disease. There can be overlap between the diseases: mutations in the same gene can lead to different renal phenotypes. It is important to know that some hereditary podocytopathies respond to therapy, whereas majority does not. For this reason, genetic testing, which is available for some hereditary podocytopathies should be performed whenever possible. This review summarizes recent progress in the eludication of genetic causes of disease and discusses their implication for the understanding of the pathogenic mechanisms which can lead to disruption of the glomerular filtration barrier.

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 Lysophosphatidic Acid Signaling in Diabetic Nephropathy

2019 ◽  
Vol 20 (11) ◽  
pp. 2850 ◽  
Author(s):  
Jong Lee ◽  
Donghee Kim ◽  
Yoon Oh ◽  
Hee-Sook Jun
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathways ◽  
Lysophosphatidic Acid ◽  
Kidney Diseases ◽  
Cell Damage ◽  
Cell Structure ◽  
Research Findings ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Function

Lysophosphatidic acid (LPA) is a bioactive phospholipid present in most tissues and body fluids. LPA acts through specific LPA receptors (LPAR1 to LPAR6) coupled with G protein. LPA binds to receptors and activates multiple cellular signaling pathways, subsequently exerting various biological functions, such as cell proliferation, migration, and apoptosis. LPA also induces cell damage through complex overlapping pathways, including the generation of reactive oxygen species, inflammatory cytokines, and fibrosis. Several reports indicate that the LPA–LPAR axis plays an important role in various diseases, including kidney disease, lung fibrosis, and cancer. Diabetic nephropathy (DN) is one of the most common diabetic complications and the main risk factor for chronic kidney diseases, which mostly progress to end-stage renal disease. There is also growing evidence indicating that the LPA–LPAR axis also plays an important role in inducing pathological alterations of cell structure and function in the kidneys. In this review, we will discuss key mediators or signaling pathways activated by LPA and summarize recent research findings associated with DN.

scholarly journals The critical role of Krüppel-like factors in kidney disease

2017 ◽  
Vol 312 (2) ◽  
pp. F259-F265 ◽  
Author(s):  
Sandeep K. Mallipattu ◽  
Chelsea C. Estrada ◽  
John C. He
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
Vital Role ◽  
Glomerular Filtration Barrier ◽  
Kidney Fibrosis ◽  
Physiological Processes ◽  
Filtration Barrier ◽  
And Function ◽  
Mammalian Embryonic Development

Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation to progression of kidney fibrosis. Seventeen members of the KLF family have been identified, and several have been well characterized in the kidney. Although they may share some overlap in their downstream targets, their structure and function remain distinct. This review highlights our current knowledge of KLFs in the kidney, which includes their pattern of expression and their function in regulating key biological processes. We will also critically examine the currently available literature on KLFs in the kidney and offer some key areas in need of further investigation.

scholarly journals On the contribution of immune 42 mechanisms to the pathogenesis of diabetic nephropathy

1996 ◽  
Vol 42 (5) ◽  
pp. 42-47
Author(s):  
О. I. Kamayeva ◽  
V. V. Sura
Keyword(s):  
Renal Failure ◽  
Diabetic Nephropathy ◽  
Western Europe ◽  
Kidney Tissue ◽  
The United States ◽  
Chronic Hemodialysis ◽  
Patients With Diabetes ◽  
End Stage ◽  
The Cost

Diabetic nephropathy (NF) came first among all the specified causes of end-stage renal failure. Patients with type 1 diabetes mellitus (DM) make up more than half of all patients treated with chronic hemodialysis in the United States and Western Europe. Among patients with diabetes with terminal renal failure, 60% are people over 50 years old, so hemodialysis is not always prescribed. However, hemodialysis is increasingly used in elderly and senile patients; therefore, the proportion of patients with diabetes, especially type II diabetes, in hemodialysis centers will increase, significantly increasing the cost of treating diabetes. Currently, along with metabolic, hemodynamic and genetic theories, the role of immune disorders in the formation and progression of DNs is being discussed. The prerequisites for the formation of a hypothesis about the immune genesis of DNs were the frequent detection of increased levels of circulating immune complexes (CICs) and immunoglobulins in the blood, as well as deposits of immunoglobulins and complement in the kidney structures of patients with diabetes. However, among researchers there is no unanimity in the explanation of these facts. Many consider indisputably existing immune abnormalities inherent in DN as non-specific epiphenomes. The immune hypothesis of the pathogenesis of DN was formulated back in the 70s. The currently accumulated data suggest the participation of the immunocomplex mechanism in the development of DN. Immunofluorescence examination of the kidney tissue of patients with diabetes almost always reveals a luminescence of IgG, IgM, less often IgA, SZ and other complement fractions along the basal membranes of the glomeruli (BMC) and tubules of focal granular and linear in nature.

scholarly journals Targeting VE-PTP phosphatase protects the kidney from diabetic injury

2019 ◽  
Vol 216 (4) ◽  
pp. 936-949 ◽  
Author(s):  
Isabel A. Carota ◽  
Yael Kenig-Kozlovsky ◽  
Tuncer Onay ◽  
Rizaldy Scott ◽  
Benjamin R. Thomson ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Tyrosine Phosphatase ◽  
Hypoxia Inducible Factor ◽  
Cell Loss ◽  
Tie2 Receptor ◽  
Nuclear Exclusion ◽  
Promising Therapeutic Target ◽  
End Stage ◽  
And Function

Diabetic nephropathy is a leading cause of end-stage kidney failure. Reduced angiopoietin-TIE2 receptor tyrosine kinase signaling in the vasculature leads to increased vascular permeability, inflammation, and endothelial cell loss and is associated with the development of diabetic complications. Here, we identified a mechanism to explain how TIE2 signaling is attenuated in diabetic animals. Expression of vascular endothelial protein tyrosine phosphatase VE-PTP (also known as PTPRB), which dephosphorylates TIE2, is robustly up-regulated in the renal microvasculature of diabetic rodents, thereby reducing TIE2 activity. Increased VE-PTP expression was dependent on hypoxia-inducible factor transcriptional activity in vivo. Genetic deletion of VE-PTP restored TIE2 activity independent of ligand availability and protected kidney structure and function in a mouse model of severe diabetic nephropathy. Mechanistically, inhibition of VE-PTP activated endothelial nitric oxide synthase and led to nuclear exclusion of the FOXO1 transcription factor, reducing expression of pro-inflammatory and pro-fibrotic gene targets. In sum, we identify inhibition of VE-PTP as a promising therapeutic target to protect the kidney from diabetic injury.

scholarly journals C-reactive protein as predictor of death in end-stage diabetic nephropathy: Role of peripheral arterial disease

2005 ◽  
Vol 68 (1) ◽  
pp. 217-227 ◽  
Author(s):  
Carsten A. Boger ◽  
Angela Gotz ◽  
Mike Stubanus ◽  
Bernhard Banas ◽  
Martina Deinzer ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Peripheral Arterial ◽  
End Stage

Remission of diabetic nephropathy in type 2 diabetic Asian population: role of tight glucose and blood pressure control

2011 ◽  
Vol 41 (8) ◽  
pp. 870-878 ◽  
Author(s):  
Ming-Chia Hsieh ◽  
Yi-Ting Hsieh ◽  
Tzu-Jung Cho ◽  
Jung-Fu Chen ◽  
Shi-Dou Lin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Blood Pressure Control ◽  
Asian Population ◽  
Pressure Control ◽  
Type 2 Diabetic

scholarly journals Recent advances in managing and understanding diabetic nephropathy

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1044 ◽  
Author(s):  
Sydney C.W. Tang ◽  
Gary C.W. Chan ◽  
Kar Neng Lai
Keyword(s):  
Diabetic Nephropathy ◽  
Management Strategies ◽  
Standard Of Care ◽  
Pressure Control ◽  
Review Article ◽  
Therapeutic Approaches ◽  
Current Standard ◽  
Developed Economies ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is the commonest cause of end-stage renal disease in most developed economies. Current standard of care for diabetic nephropathy embraces stringent blood pressure control via blockade of the renin-angiotensin-aldosterone system and glycemia control. Recent understanding of the pathophysiology of diabetic nephropathy has led to the development of novel therapeutic options. This review article focuses on available data from landmark studies on the main therapeutic approaches and highlights some novel management strategies.

scholarly journals Inflammation in Diabetic Nephropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Andy K. H. Lim ◽  
Gregory H. Tesch
Keyword(s):  
Diabetic Nephropathy ◽  
Cell Signalling ◽  
Inflammatory Cells ◽  
Mitogen Activated Protein Kinase ◽  
Amino Terminal ◽  
Human Diabetes ◽  
Mitogen Activated Protein ◽  
Experimental Approaches ◽  
End Stage

Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly infiltrating macrophages, T-lymphocytes and the subpopulation of regulatory T cells. The possible link between immune deposition and diabetic nephropathy is explored, along with the recently described immune complexes of anti-oxidized low-density lipoproteins. We also briefly discuss some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines. Lastly, we present the latest data on the pathogenic role of the stress-activated protein kinases in diabetic nephropathy, from studies on the p38 mitogen activated protein kinase and the c-Jun amino terminal kinase cell signalling pathways. The genetic and pharmacological approaches which reduce inflammation in diabetic nephropathy have not only enhanced our understanding of the pathophysiology of the disease but shown promise as potential therapeutic strategies.

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