scholarly journals New Endothelial Mechanisms in Glomerular (Patho)biology and Proteinuria Development Captured by Intravital Multiphoton Imaging

2021 ◽  
Vol 8 ◽  
Author(s):  
Georgina Gyarmati ◽  
Chaim O. Jacob ◽  
János Peti-Peterdi

In the past two decades, intravital imaging using multiphoton microscopy has provided numerous new visual and mechanistic insights into glomerular biology and disease processes including the function of glomerular endothelial cells (GEnC), podocytes, and the development of proteinuria. Although glomerular endothelial injury is known to precede podocyte damage in several renal diseases, the primary role of GEnCs in proteinuria development received much less attention compared to the vast field of podocyte pathobiology. Consequently, our knowledge of GEnC mechanisms in glomerular diseases is still emerging. This review highlights new visual clues on molecular and cellular mechanisms of GEnCs and their crosstalk with podocytes and immune cells that were acquired recently by the application of multiphoton imaging of the intact glomerular microenvironment in various proteinuric disease models. New mechanisms of glomerular tissue remodeling and regeneration are discussed based on results of tracking the fate and function of individual GEnCs using serial intravital multiphoton imaging over several days and weeks. The three main topics of this review include (i) the role of endothelial injury and microthrombi in podocyte detachment and albumin leakage via hemodynamic and mechanical forces, (ii) the alterations of the endothelial surface layer (glycocalyx) and its interactions with circulating immune cells in lupus nephritis, and (iii) the structural and functional remodeling and regeneration of GEnCs in hypertension, diabetes, and other experimental injury conditions. By the comprehensive visual portrayal of GEnCs and the many other contributing glomerular cell types, this review emphasizes the complexity of pathogenic mechanisms that result in proteinuria development.

2019 ◽  
Vol 9 (2) ◽  
pp. 1571-1579
Author(s):  
Gopi Aryal ◽  
Sameer Chhetri Aryal

Diverse pathogenetic mechanisms and clinical manifestation of renal diseases may produce the same renal morphologic pattern or variety of renal morphologic pattern can lead to the same clinical syndrome. The primary role of the renal biopsy is to provide a diagnosis and information about disease activity and chronicity. The systematic approach to native medical renal biopsy includes evaluation of the four compartments of the kidney sequentially (glomeruli, tubules, interstitium, and blood vessels). The diagnosis in renal pathology is an integrated process in which we must analyze all clinical data, light microscopy, immunohistology, and electron microscopy studies for diagnosis. The aim of the article is to describe the handling of the renal tissue in the anatomical pathology laboratory. It also provides the guideline to renal biopsy evaluation and approach to arrive at the diagnosis of glomerular diseases with similar clinical presentations.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2141
Author(s):  
Katie Alexander ◽  
Charles O. Elson

Bacteria and mammals have co-evolved with one another over millennia, and it has become impossible to interpret mucosal immunity without taking the microbiota into consideration. In fact, the primary role of the mucosal immune system is regulating homeostasis and the host relationship with the microbiota. Bacteria are no longer seen as simply invading pathogens, but rather a necessary component to one’s own immune response. On the one hand, the microbiota is a vital educator of immune cells and initiator of beneficial responses; but, on the other, dysbiosis of microbiota constituents are associated with inflammation and autoimmune disorders. In this review, we will consider recent advances in the understanding of how the microbiota influences host mucosal immunity, particularly the initial development of the immune response and its implications.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Xin Ye ◽  
Xu-jie Zhou ◽  
Hong Zhang

Autophagy is an important biology process, central to the maintenance of biology process in both physiological and pathological situations. It is regarded as a “double-edged sword”—exerting both protective and/or detrimental effects. These two-way effects are observed in immune cells as well as renal resident cells, including podocytes, mesangial cells, tubular epithelial cells, and endothelial cells of the glomerular capillaries. Mounting evidence suggests that autophagy is implicated in the pathological process of various immune-related renal diseases (IRRDs) as well as the kidney that underwent transplantation. Here, we provide an overview of the pathological role of autophagy in IRRDs, including lupus nephritis, IgA nephropathy, membrane nephropathy, ANCA-associated nephritis, and diabetic nephropathy. The understanding of the pathogenesis and regulatory mechanisms of autophagy in these renal diseases may lead to the identification of new diagnostic targets and refined therapeutic modulation.


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.


2018 ◽  
Vol 29 (7) ◽  
pp. 714-719 ◽  
Author(s):  
Joana Gameiro ◽  
Sofia Jorge ◽  
José A Lopes

The presence of human immunodeficiency virus (HIV)-related kidney disease is an important cause of mortality and morbidity. HIV infection induces renal injury by direct cytotoxicity or immune complex-mediated glomerulonephritis in patients with genetic susceptibility factors. In the last decades, with the development and diffusion of combination antiretroviral therapy, which has prolonged patient survival, there has been a shift in the spectrum of renal diseases in HIV-infected patients, with the decrease of glomerular diseases and increase in the role of nephrotoxicity and co-morbidities. This review provides a contemporary and critical review on the main renal syndromes occurring in HIV-infected patients.


1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.


2018 ◽  
Vol 5 (1) ◽  
pp. 93-115
Author(s):  
Miloš Stamenković

SummarySports photography undoubtedly has a significant place in sports press and publicism. It’s main and primary role is to present sports to the readers as art, which it is. Sport is characterized by dynamic and varied movements, and the main role of sports photography is reflected in the fact that it is in this way that sport shows its essence. Having in mind that photography tells more than a thousand words it sends a clear message to the reader as well to people who are informed about events via sports portals. Sports photography is a multidimensional art for many reasons. When we say “multi”, it primarily refers to a wider range that sports photography has to offer, which means sports photography is not only directed at presenting athletes on the move and the main actors who contribute to achieving the results by their engagement – it also has the role of sports “psychophotography” which is an analysis and capture of the emotional reaction of an athlete after winning or losing from the opposing team.


Author(s):  
A.V. GOLUBEV ◽  

The diffusion of innovations is described as a process in a number of scientific papers. At the same time, the causes of this process have not been sufficiently studied. The author’s goal is to consider the main regularities, under which the life cycle of innovations begins, and propose measures to enhance diffusion in modern conditions. As a scientific hypothesis, the author accepts the postulate about the primary role of the obolescence of attracted innovations in this process. The analysis revealed not only the economic proportions that initiate the start of innovation promotion, but also the influence on the diffusion rate of the obsolescence degree of innovations and the market share occupied by the new product. Methodological approaches have been developed to determine economic efficiency depending on the moment of technological change-over, as well as to determine the absolute and relative speed of innovation diffusion. Sociological studies were conducted to determine the state of innovation development and the time lag between obtaining information about an innovation and its practical implementation. The author presents his “Agroopyt” information system developed to disseminate knowledge in the agricultural sphere and ensure technology transfer in agriculture. Digital methods provide for significant accelerateion of the diffusion of innovations and expand its scope.


2018 ◽  
Vol 25 (7) ◽  
pp. 793-801 ◽  
Author(s):  
Helene Francois ◽  
Lola Lecru

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