Potential role of extracellular vesicles in the pathophysiology of glomerular diseases

2020 ◽  
Vol 134 (20) ◽  
pp. 2741-2754
Author(s):  
Xia-Qing Li ◽  
Lilach O. Lerman ◽  
Yu Meng

Abstract Extracellular vesicles (EVs) are membrane-bound vesicles released by most cells and are found in diverse biological fluids. The release of EVs provides a new mechanism for intercellular communication, allowing cells to transfer their functional cargoes to target cells. Glomerular diseases account for a large proportion of end-stage renal disease (ESRD) worldwide. In recent years, an increasing number of research groups have focused their effort on identifying the functional role of EVs in renal diseases. However, the involvement of EVs in the pathophysiology of glomerular diseases has not been comprehensively described and discussed. In this review, we first briefly introduce the characteristics of EVs. Then, we describe the involvement of EVs in the mechanisms underlying glomerular diseases, including immunological and fibrotic processes. We also discuss what functions EVs derived from different kidney cells have in glomerular diseases and how EVs exert their effects through different signaling pathways. Furthermore, we summarize recent advances in the knowledge of EV involvement in the pathogenesis of various glomerular diseases. Finally, we propose future research directions for identifying better management strategies for glomerular diseases.

2021 ◽  
pp. 353-382
Author(s):  
Gopesh K. Modi ◽  
Vivekanand Jha

Assessing renal function, Urinalysis, Proteinuria, Hematuria, Chyluria, Imaging in renal disease, Kidney biopsy, Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy, End Stage Renal Disease and Dialysis, Kidney Transplantation, Glomerular diseases, Acute glomerulonephritis, Urinary schistosomiasis (bilharzia), Infections and Kidney Disease, Rapidly Progressive glomerulonephritis, Tubulointerstitial Disease, Urinary Tract Infection, Vesico-ureteric reflux, Renal Stones, Renal Disease in Pregnancy, Renal Artery Stenosis, Renal Mass, Inherited Renal Diseases


2019 ◽  
Vol 20 (14) ◽  
pp. 3567 ◽  
Author(s):  
Teresa Seccia ◽  
Brasilina Caroccia ◽  
Maria Piazza ◽  
Gian Paolo Rossi

Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the ‘classic’ view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.


2020 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Jennifer L Holmes ◽  
Alexandre Biella ◽  
Timothy Morck ◽  
Jena Rostorfer ◽  
Barbara Schneeman

ABSTRACT On August 13–14, 2019, the Healthcare Nutrition Council and the ASN held the Medical Foods Workshop: Science, Regulation, and Practical Aspects. Medical food products help patients manage their disease and improve their quality of life. Yet many hurdles exist to getting patients new products. In this workshop, participants addressed some of these hurdles, with specific emphasis on topics like the statutory term distinctive nutritional requirements, the regulatory term modification of the diet alone, the role of clinical guidelines, the requirement that medical foods be used under medical supervision, and differentiation of foods for special dietary use from medical foods, as well as product innovation and future research. Real-world examples were discussed for intractable epilepsy, diabetes, end-stage renal disease, and inflammatory bowel disease.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jonathan M. Carnino ◽  
Zhi Hao Kwok ◽  
Yang Jin

Extracellular vesicles are membrane-bound nanoparticles secreted by cells which play a well-known role in cell to cell communication. The most update to date nomenclature categorizes extracellular vesicles based on their relative size, protein markers, and/or the cell type of origin. Extracellular vesicles can be isolated from biological fluids using a variety of methods, including but not limited to, ultrafiltration, size-exclusion chromatography, differential ultracentrifugation, density gradient centrifugation, precipitation-based methods, and immunoaffinity capture. These nanovesicles carry distinct “cargo,” made up of biomolecules such as nucleic acids, lipids, and protein, which is delivered to nearby target cells. The “cargo” profile carried by extracellular vesicles is critical in their role of communication and resembles the physiological status of the cell they originated from. For the purpose of this review, we will focus on the miRNA cargo. Extracellular vesicle-miRNA profiles hold the potential to be used in diagnostic panels for a variety of diseases through a novel method known as “liquid biopsy.” In addition to this, extracellular vesicles may serve as a potential method to deliver drugs to specific cells within the body. This mini-review provides background into what extracellular vesicles are, methods of isolating these nanoparticles, their potential use as a biomarker and drug delivery system for precision medicine, and a summary of the current literature covering the role of some extracellular vesicle-cargo's in various pulmonary diseases.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yu Zhang ◽  
Jie Wang ◽  
Jianhua Zhou

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS), a podocytopathy, is one of the most common primary glomerular diseases causing end-stage renal disease in children. Its mechanisms remain unclear and the effective treatment lacks. MiR-155 is a typical multifunctional miRNA, which serves a crucial role in the regulation of numerous vessel cells. The present study aimed to investigate the role of miR-155 in the pathogenesis of FSGS. Method A FSGS model was establishe by injection of adriamycin in miR-155 knockout mice. Renal pathological changes were observed by Periodic Schiff-Methenamine Silver staining and Masson trichrome staining. Podocyte morphology and autophagosomes were examined with electron microscopy. Podocyte density was estimated by the Weibel-Gomez method. Expression of autophagy markers and apoptosis-associated proteins were analyzed by Western blotting analysis. Results Silencing of miR-155 significantly decreased urinary protein excretion and ameliorated glomerulosclerosis in adriamycin-induced FSGS mice. We found that adriamycin treatment led to fusion of podocyte foot processes, swelling of the podocyte body, dilated mitochondria, and podocyte loss. Inhibition of miR-155 improved podocyte depletion and the above cytopathies induced by adriamycin. In addition, the results also demonstrated that in miR-155 KO mice, the expression of LC3 and ATG5 was increased and the expression of P62 was decreased. Conclusion These suggest that modulated miR-155 can prevent podocyte damage, by regulating the level of autophagy. The present study provides a novel insight into microRNAs as potential therapeutics for the treatment of podocytopathy.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1741
Author(s):  
Mayra Paolillo ◽  
Sergio Comincini ◽  
Sergio Schinelli

Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV “delivery code” and on the combinations of the hypothesized EV surface membrane “sender” and “recipient” molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.


2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.


2021 ◽  
Vol 10 (10) ◽  
pp. 2046
Author(s):  
Goren Saenz-Pipaon ◽  
Saioa Echeverria ◽  
Josune Orbe ◽  
Carmen Roncal

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.


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