scholarly journals Sphingosine-1-Phosphate Metabolism and Signaling in Kidney Diseases

2020 ◽  
Vol 32 (1) ◽  
pp. 9-31
Author(s):  
Yelena Drexler ◽  
Judith Molina ◽  
Alla Mitrofanova ◽  
Alessia Fornoni ◽  
Sandra Merscher
Keyword(s):  
Structural Integrity ◽  
Kidney Diseases ◽  
Second Messengers ◽  
Proper Function ◽  
Renal Cells ◽  
Glomerular Filtration Barrier ◽  
The Past ◽  
Filtration Barrier ◽  
Sphingosine 1 Phosphate

In the past few decades, sphingolipids and sphingolipid metabolites have gained attention because of their essential role in the pathogenesis and progression of kidney diseases. Studies in models of experimental and clinical nephropathies have described accumulation of sphingolipids and sphingolipid metabolites, and it has become clear that the intracellular sphingolipid composition of renal cells is an important determinant of renal function. Proper function of the glomerular filtration barrier depends heavily on the integrity of lipid rafts, which include sphingolipids as key components. In addition to contributing to the structural integrity of membranes, sphingolipid metabolites, such as sphingosine-1-phosphate (S1P), play important roles as second messengers regulating biologic processes, such as cell growth, differentiation, migration, and apoptosis. This review will focus on the role of S1P in renal cells and how aberrant extracellular and intracellular S1P signaling contributes to the pathogenesis and progression of kidney diseases.

Acid ceramidase, a double-edged sword in cancer aggression: A minireview

2020 ◽  
Vol 20 ◽  
Author(s):  
Helen Shiphrah Vethakanraj ◽  
Niveditha Chandrasekaran ◽  
Ashok Kumar Sekar
Keyword(s):  
Cell Fate ◽  
Cancer Progression ◽  
Potential Role ◽  
Tumour Progression ◽  
Acid Ceramidase ◽  
The Core ◽  
The Past ◽  
Sphingosine 1 Phosphate ◽  
Key Enzyme

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.

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 The Protective Effect of Shen Qi Wan on Adenine-Induced Podocyte Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yiyou Lin ◽  
Jieying Zhang ◽  
Yunbo Fu ◽  
Liting Ji ◽  
Luning Lin ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Kidney Injury ◽  
Glomerular Filtration Barrier ◽  
Podocyte Injury ◽  
Nitrogen Levels ◽  
Filtration Barrier ◽  
Transmission Electron ◽  
High Level ◽  
Food Processes

Podocytes are a special type of differentiated epithelial cells that maintain the glomerular filtration barrier in the kidney. Injury or damages in podocytes can cause kidney-related disorders, like CKD. The injury or dysfunction of podocytes can occur by different metabolic disorders. Due to the severity and complexity of podocyte injuries, this state is considered as a serious health issue worldwide. Here, we examined and addressed the efficacy of an alternative Chinese medicine, Shen Qi Wan (SQW), on podocyte-related kidney injury. We evaluated the role and mechanism of action of SQW in podocyte injury. We observed that SQW significantly reduced 24-hour urinary protein and blood urea nitrogen levels and alleviated the pathological damage caused by adenine. Moreover, SQW significantly decreased the expression of nephrin and increased the expression of WT1 and AQP1 in the kidney of mice treated with adenine. We observed that SQW did not effectively reduce the high level of proteinuria in AQP1−/− mice indicating the prominent role of AQP1 in the SQW-ameliorating pathway. Transmission electron microscopy (TEM) images indicated the food processes effacement in AQP1−/− mice were not lessened by SQW. In conclusion, podocyte injury could alter the pathological nature of the kidney, and SQW administration relieves the nature of pathogenesis by activating AQP1.

scholarly journals Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier

2020 ◽  
Vol 318 (6) ◽  
pp. F1520-F1530
Author(s):  
Kozue Uchio-Yamada ◽  
Keiko Yasuda ◽  
Yoko Monobe ◽  
Ken-ichi Akagi ◽  
Osamu Suzuki ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Dependent Manner ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Gbm Thickening ◽  
Strain Dependent ◽  
Deficient Mice

Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies have revealed that Tns2-deficient mice exhibit defects of the glomerular basement membrane (GBM) soon after birth in a strain-dependent manner. However, the mechanisms for the onset of defects caused by Tns2 deficiency remains unidentified. Here, we aimed to determine the role of Tns2 using newborn Tns2-deficient mice and murine primary podocytes. Ultrastructural analysis revealed that developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin-α2 accumulation followed by GBM thickening. In addition, analysis of primary podocytes revealed that Tns2 deficiency led to impaired podocyte-GBM interaction and massive expression of laminin-α2 in podocytes. Our study suggests that weakened podocyte-GBM interaction due to Tns2 deficiency causes increased mechanical stress on podocytes by continuous daily filtration after birth, resulting in stressed podocytes ectopically producing laminin-α2, which interrupts GBM processing. We conclude that Tns2 plays important roles in the podocyte-GBM interaction and maintenance of the glomerular filtration barrier.

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 A new function for parietal epithelial cells: a second glomerular barrier

2009 ◽  
Vol 297 (6) ◽  
pp. F1566-F1574 ◽  
Author(s):  
Takamoto Ohse ◽  
Alice M. Chang ◽  
Jeffrey W. Pippin ◽  
George Jarad ◽  
Kelly L. Hudkins ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Basement Membrane ◽  
Glomerular Filtration ◽  
Glomerular Filtration Barrier ◽  
Impermeable Barrier ◽  
Filtration Barrier ◽  
Proximal Tubular ◽  
Parietal Epithelial Cells ◽  
Glomerular Barrier

The functional role of glomerular parietal epithelial cells (PECs) remains poorly understood. To test the hypothesis that PECs form an impermeable barrier to filtered protein through the formation of tight junctions (TJ), studies were performed in normal animals and in the anti-glomerular basement membrane (GBM) model of crescentic nephritis. Electron microscopy showed well-defined TJ between PECs in normal mice, which no longer could be identified when these cells became extensively damaged or detached from their underlying Bowman's basement membrane. The TJ proteins claudin-1, zonula occludens-1, and occludin stained positive in PECs; however, staining decreased in anti-GBM disease. To show that these events were associated with increased permeability across the PEC-Bowman's basement membrane barrier, control and diseased animals were injected intravenously with either Texas red-conjugated dextran (3 kDa) or ovalbumin (45 kDa) tracers. As expected, both tracers were readily filtered across the glomerular filtration barrier and taken up by proximal tubular cells. However, when the glomerular filtration barrier was injured in anti-GBM disease, tracers were taken up by podocytes and PECs. Moreover, tracers were also detected between PECs and the underlying Bowman's basement membrane, and in many instances were detected in the extraglomerular space. We propose that together with its underlying Bowman's basement membrane, the TJ of PECs serve as a second barrier to protein. When disturbed following PEC injury, the increase in permeability of this layer to filtered protein is a mechanism underlying periglomerular inflammation characteristic of anti-GBM disease.

scholarly journals The role of soluble urokinase-type Plasminogen Activator Receptor (suPAR) in Chronic Kidney Disease

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Ade Yonata ◽  
Ian Effendi ◽  
Zulkhair Ali ◽  
Novadian Suhaimi ◽  
S Suprapti
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Plasminogen Activator ◽  
Focal Segmental Glomerulosclerosis ◽  
Kidney Diseases ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

Kidney disease affects 800 million children and adults worldwide, and the numbers keep increasing. A better understanding of the pathogenesis in kidney diseases, especially on a biomolecular level, is much needed to identify novel biomarkers and therapeutic targets for kidney diseases. The glomerular filtration barrier comprises endothelial cells, the glomerular basement membrane, and podocytes. The podocyte has a central role in part of the glomerular filtration barrier. The nor­mal functioning of podocytes is particularly important in preventing the heavy proteinuria seen in nephrotic syndrome or diabetic nephropathy, or in the disease process of focal segmental glomerulosclerosis. The podocyte is injured by circulating factors, which final­ly results in deranged podocyte motility. Soluble uro­kinase-type plasminogen activator receptor (suPAR) is a circulating form of glycosyl-phosphatidylinositol uPAR domain membrane protein and is known to play a role in the pathogenesis in kidney diseases, specifi­cally focal segmental glomerulosclerosis and diabetic nephropathy. suPAR binds to αvβ3 integrin on podo­cyte foot processes and causes podocyte structure dis­organization leading to glomerular filtration disruption and hence proteinuria. suPAR is also a potential bio­marker to predict the incidence of CKD.

scholarly journals SP064THE ROLE OF TRYPTOPHAN METABOLISM IN MAINTAINING THE INTEGRITY OF THE GLOMERULAR FILTRATION BARRIER

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i107-i107
Author(s):  
Patricia Bolanos-Palmieri ◽  
Konstantin Deutsch ◽  
Hermann Haller ◽  
Patricia Schroder ◽  
Lynne Staggs ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Tryptophan Metabolism ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier

scholarly journals Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Marco Ragusa ◽  
Cristina Barbagallo ◽  
Duilia Brex ◽  
Angela Caponnetto ◽  
Matilde Cirnigliaro ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Structural Integrity ◽  
Current Knowledge ◽  
Noncoding Rnas ◽  
Special Focus ◽  
Cellular Mechanisms ◽  
Protein Coding ◽  
The Past ◽  
Higher Eukaryotes

Over the past few years, noncoding RNAs (ncRNAs) have been extensively studied because of the significant biological roles that they play in regulation of cellular mechanisms. ncRNAs are associated to higher eukaryotes complexity; accordingly, their dysfunction results in pathological phenotypes, including cancer. To date, most research efforts have been mainly focused on how ncRNAs could modulate the expression of protein-coding genes in pathological phenotypes. However, recent evidence has shown the existence of an unexpected interplay among ncRNAs that strongly influences cancer development and progression. ncRNAs can interact with and regulate each other through various molecular mechanisms generating a complex network including different species of RNAs (e.g., mRNAs, miRNAs, lncRNAs, and circRNAs). Such a hidden network of RNA-RNA competitive interactions pervades and modulates the physiological functioning of canonical protein-coding pathways involved in proliferation, differentiation, and metastasis in cancer. Moreover, the pivotal role of ncRNAs as keystones of network structural integrity makes them very attractive and promising targets for innovative RNA-based therapeutics. In this review we will discuss: (1) the current knowledge on complex crosstalk among ncRNAs, with a special focus on cancer; and (2) the main issues and criticisms concerning ncRNAs targeting in therapeutics.

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