Role of Inflammatory Cells on Injury and Regeneration of the Kidney
Author : Manuela Ghielli
Publisher :
Page : 209 pages
File Size : 30,44 MB
Release : 1999
Category :
ISBN :
Author : Manuela Ghielli
Publisher :
Page : 209 pages
File Size : 30,44 MB
Release : 1999
Category :
ISBN :
Author : Patrick C. Baer
Publisher : MDPI
Page : 496 pages
File Size : 13,43 MB
Release : 2020-04-03
Category : Medical
ISBN : 3039285386
Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of subsequent chronic kidney disease. Although the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function is urgently needed. The Special Issue covers research articles that investigated the molecular mechanisms of inflammation and injury during different renal pathologies, renal regeneration, diagnostics using new biomarkers, and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models. The Special Issue contains important reviews that consider the current knowledge of cell death and regeneration, inflammation, and the molecular mechanisms of kidney diseases. In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells or their derivates is summarized. This edition is complemented by reviews that deal with the current data situation on other specific topics like diabetes and diabetic nephropathy or new therapeutic targets.
Author : Patrick C. Baer
Publisher :
Page : 496 pages
File Size : 21,86 MB
Release : 2020
Category : Internal medicine
ISBN : 9783039285396
Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of subsequent chronic kidney disease. Although the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function is urgently needed. The Special Issue covers research articles that investigated the molecular mechanisms of inflammation and injury during different renal pathologies, renal regeneration, diagnostics using new biomarkers, and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models. The Special Issue contains important reviews that consider the current knowledge of cell death and regeneration, inflammation, and the molecular mechanisms of kidney diseases. In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells or their derivates is summarized. This edition is complemented by reviews that deal with the current data situation on other specific topics like diabetes and diabetic nephropathy or new therapeutic targets.
Author : Patrick C Baer
Publisher : Mdpi AG
Page : 318 pages
File Size : 25,95 MB
Release : 2021-11-23
Category :
ISBN : 9783036523705
Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of chronic kidney disease in the sequel. Whereas the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function-in both the short- and long-term-is urgently needed. This Special Issue includes papers investigating the pathological mechanisms of renal inflammation and AKI and diagnostics using new biomarkers. Furthermore, experimental in vitro and in vivo studies examining potential new approaches to attenuate kidney dysfunction are included, as well as review articles.
Author : Patrick C. Baer
Publisher :
Page : 318 pages
File Size : 33,90 MB
Release : 2021
Category :
ISBN : 9783036523699
Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of chronic kidney disease in the sequel. Whereas the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function--in both the short- and long-term--is urgently needed. This Special Issue includes papers investigating the pathological mechanisms of renal inflammation and AKI and diagnostics using new biomarkers. Furthermore, experimental in vitro and in vivo studies examining potential new approaches to attenuate kidney dysfunction are included, as well as review articles.
Author : Yoshio Terada
Publisher : Springer Nature
Page : 390 pages
File Size : 19,97 MB
Release : 2020-05-14
Category : Medical
ISBN : 981151108X
This book presents up-to-date information on the clinical-pathophysiological features of acute renal injury and discusses the KDIGO diagnostic criteria, as well as novel experimental findings, including in the area of regenerative medicine. It also highlights the clinical-pathophysiological importance of AKI in clinical settings, including differential diagnoses and management of AKI. In the past, the pathology associated with sudden renal impairment was characterized as acute renal failure (ARF). However, in the 2000s, the joint efforts of specialists in fields including nephrology, intensive care medicine, and cardiovascular medicine led to the introduction of a novel concept known as acute kidney injury (AKI). As medical care progressed, patients such as high-risk elderly subjects who were not deemed to be candidates for invasive therapy came to be treated in intensive care units (ICUs). As a result, kidney injury as a subset of multiple organ failure was re-considered as AKI, especially in intensive care medicine. AKI was then proposed as a novel disease concept to emphasize the importance of early diagnosis and early intervention to improve prognosis.Presenting novel features, such as the definition of AKI, risk factors and management; biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP); long-term outcomes of AKI; as well as renal regeneration using iPS cell, manipulation of embryonic genes, and Xenotransplanted embryonic kidney, this book is of interest to all physicians and researchers in this field around the globe.
Author : Wei Jing Liu
Publisher : Frontiers Media SA
Page : 237 pages
File Size : 15,30 MB
Release : 2024-08-30
Category : Medical
ISBN : 2832553648
Kidney disease is a leading cause of death worldwide and is increasingly recognized as a global health problem. The kidneys are a frequent target of systemic immune and autoimmune disorders, including systemic autoimmunity and vasculitis, immune complex-related serum sickness, and complement disorders. The complex regulation between the immune system and inflammation plays a key role in the progression of kidney disease, especially in immune-related nephropathy. Cytokines released by monocytes/macrophages, including IL-17, INF-γ, TNF, and IL-6, exacerbate renal dysfunction and injury. M1 pro-inflammatory cells help to clear infections but can also promote renal injury and lead to renal fibrosis. Loss of immune homeostasis can exacerbate the adverse effects of inflammation on the kidney and lead to loss of renal function. Therefore, further understanding of immune dysregulation and inflammatory responses has the potential to develop innovative, paradigm-shifting strategies for the treatment of kidney disease. The development of novel computational tools and genomic data analysis are accelerating our understanding of the crosstalk of immunity and inflammation in kidney disease. The aim of this Research Topic is to provide a forum to explore potential and effective therapeutic targets by focusing on the role of regulatory mechanisms of immunity and inflammation in renal disease. We aim to elucidate the possible biological mechanisms of immunity and inflammation in the pathogenesis of kidney disease. We welcome submissions of Original Research and Review articles, including but not limited to the following: (1) The role of immune regulation of inflammation in immune-related nephropathy. (2) Mechanisms of immune and inflammatory interactions in hypertensive nephropathy. (3) Emerging novel cytokines and immune markers in the diagnosis and prognosis of membranous nephropathy. (4) Pathogenetic mechanism of inflammation in chronic kidney disease. (5) Influence of chemokines and chemokine receptors on inflammation in kidney disease.
Author : Timothy Michael Williams
Publisher :
Page : 294 pages
File Size : 32,7 MB
Release : 2014
Category :
ISBN :
Kidney disease is a major health concern, affecting a growing number of people and placing an enormous burden on health care systems worldwide. There is no cure for kidney disease and the current treatments heavily impact patient quality of life. However, the kidneys possess a limited capacity to regenerate, which provides hope for the future development of treatments aimed at promoting endogenous repair. This approach, however, will not be without challenges, due to the broad range of kidney diseases arising from different aetiologies.The macrophage is a myeloid cell type recognised for its roles in both inflammation and tissue repair. Originally identified as a contributor to innate host defence, these cells are now known to also possess immunomodulatory and wound healing capabilities. For these reasons, manipulating macrophage function may help promote endogenous repair in damaged kidneys. Recent attempts to define macrophage activation states as either classical (M1) or alternative (M2) have been useful, although this classification system appears too simplistic, due in part to the complexity of the in vivo environment during injury and disease, where macrophages receive a broad and changing range of stimuli. Therefore, this thesis presents a series of studies that examine the contribution of myeloid cells to the initial inflammatory phase and subsequent resolution/remodelling phase of experimental ischaemia/reperfusion (IR) injury, a model of acute kidney injury (AKI).Chapter Two describes the establishment of a flow cytometry protocol for detecting and analysing myeloid cells in injured and non-injured kidneys. This involved optimising enzymatic digestion methods and identifying important monocyte and macrophage subpopulations, in addition to neutrophils and epithelial cells in the context of IR injury. Chapter Three utilised these methods to comprehensively characterise myeloid populations, inflammatory cytokines and epithelial cell loss throughout the initiation and resolution phases of kidney IR injury. The histopathology corresponding to each of the time-points was also examined. Finally, Chapter Four explored and compared the effects of granulocyte macrophage-colony stimulating factor (GM-CSF) and colony stimulating factor-1 receptor (CSF-1R) blockade, using neutralising antibodies, on IR-mediated damage and repair. GM-CSF and CSF-1 are principal myeloid growth factors linked to pathogenesis and repair in a range of diseases. The effects on different cell types, serum cytokines, collagen content and renal function were assessed. While GM-CSF and CSF-1R blockade were able to reduce a number of inflammatory mediators, the benefits were outweighed by impacts on reparative subpopulations of myeloid cells. In particular, CSF-1R blockade substantially reduced infiltrating inflammatory monocytes shortly following injury but also depleted mannose receptor (MR) expressing M2 macrophages. The prolonged administration of this antibody also resulted in a significant increase in the total collagen content at 14 days post-IR injury.Monocyte-derived macrophages contribute to the pathogenesis of IR injury but are also crucial mediators of kidney remodelling. Therefore, selective/targeted depletion or manipulation of specific myeloid populations may be beneficial in reducing inflammation-mediated damage, whilst still allowing reparative subpopulations to resolve tissue damage, promote tubular regeneration and mediate tissue remodelling.
Author : Michael S. Goligorsky
Publisher : Academic Press
Page : 473 pages
File Size : 33,4 MB
Release : 2010-11-26
Category : Science
ISBN : 0123809290
Progression of chronic diseases in general and chronic kidney disease in particular has been traditionally viewed in the light of various contributors to development of glomerulosclerosis and tubulointerstitial scarring culminating in renal fibrosis. Indeed, this dogma prevailed for decades underscoring experimental attempts to halt fibrotic processes. Breakthrough investigations of the past few years on stem/progenitor cell involvement in organ regeneration caused a conceptual shift in tackling the mechanisms of nephrosclerosis. It has become clear that the rate of progression of chronic kidney disease is the net sum of the opposing trends: degenerative fibrotic processes and regenerative repair mechanisms. The latter part of this equation has been by and large ignored for years and only recently attracted investigative attention. This book revisits the problem of kidney disease by focusing on regenerative mechanisms in renal repair and on the ways these regenerative processes can become subverted by an intrinsic disease process eventuating in its progression. Cutting-edge investigations are summarized by the most experienced international team of experts. - Presents a comprehensive, translational source for all aspects of renal stem cells, tissue regeneration, and stem cell therapies for renal diseases in one reference work. This will ultimately result in time savings for academic, medical and pharma researchers - Experts in the renal stem cell system in kidney repair and regeneration take readers from the bench research to new therapeutic approaches, providing a common language for nephrology researchers, fellows and other stem cell researchers. This enables the discussion of development of stem cells and their use in the repair and regeneration of the kidney
Author : Maliha Alikhan
Publisher :
Page : 434 pages
File Size : 25,26 MB
Release : 2012
Category :
ISBN :
Kidney disease is a growing public health concern, and current therapies inflict substantial strain on both patients and the health care system. Fortunately, the adult kidney can repair itself following transient damage. While the cellular events that lead to kidney regeneration are well defined, less is understood about the endogenous repair mechanisms that control these pathways. In adult organs, macrophages display significant heterogeneity during disease progression. The surrounding microenvironment ultimately influences disease outcome via polarisation of macrophages toward a classically activated M1-like state or an alternatively activated M2-like phenotype. M1-like macrophages are a pro-inflammatory population that are involved in host defence and tissue destruction, whereas M2-like macrophages secrete anti-inflammatory mediators that induce inflammatory resolution and wound healing. In the mouse model of renal ischemia-reperfusion (IR) injury, M2-like macrophages play a fundamental role in repair by resolving inflammation and mediating the restoration of injured renal epithelial cells. Colony-stimulating factor (CSF)-1 is a hematopoietic growth factor that primarily regulates the development, proliferation and survival of macrophages. In addition, CSF-1 exhibits important pleiotropic roles during development, homeostasis, injury and cancer. Studies also demonstrate that CSF-1 can foster epithelial cell repair and tissue remodelling in animal models of acute injury. The overall aim of this thesis was to investigate the regenerative potential of CSF-1 therapy in an acute renal IR injury model, with particular attention to the functional role of M2-like macrophages. Chapter 2 reports the structural and functional kidney recovery following CSF-1 administration to mice with established IR injury. Five days after injection of CSF-1 to IR mice, increased epithelial cell proliferation and reduced intratubular cast formation and interstitial matrix expansion was evident compared to vehicle-treated mice. Structural recovery at day 7 also coincided with reduced collagen accumulation and improved functional recovery as evident by reduced urinary albumin compared to vehicle-treated mice.In Chapter 3, extensive characterisation of macrophage phenotype and function was performed to determine the functional contribution of CSF-1-mediated renal regeneration. CSF-1 influenced renal macrophage number and maturity following IR injury. The number of CSF-1-responsive macrophages increased at day 5 and then declined at day 7 when recovery was complete. This coincided with macrophage maturity with increased expression of F4/80 and MHC II at day 5 when damage was still evident followed by reduced expression at day 7. Flow cytometry and real-time PCR analysis of the expression of known M1- and M2-associated genes provided further insight into the influence of CSF-1 therapy on macrophage phenotype and function. CSF-1-responsive macrophages displayed increased expression of common M2-like genes including arginase, CCL17, scavenger receptor and macrophage mannose receptor. To further corroborate these findings, microarray analysis was performed in order to investigate the specific macrophage signalling pathways and genes involved in the CSF-1-accelerated repair response. The most significant differences in macrophage gene expression occurred at day 5 post-IR injury, where the genes differentially expressed in CSF-1-responsive macrophages were primarily associated with M2-like signalling pathways. These included the glucocorticoid receptor, IL-10 and insulin-like growth factor (IGF)-1 signalling pathways, which are important in inflammatory resolution and wound healing. Of significant interest was the differential expression of genes associated with the IGF-1 signalling pathways. IGF-1 is known to play important reparative roles in post-ischemic kidneys, and CSF-1 can also control the expression of macrophage-derived IGF-1. Further analysis and validation was therefore performed using real-time PCR analysis, which revealed increased IGF-1 expression in CSF-1-responsive macrophages at both time-points compared to vehicle-treated mice. These findings suggest that CSF-1 accelerates renal regeneration following acute IR injury via alteration of macrophage phenotype, and in part by macrophage-derived IGF-1 production. However, reports from other investigators also indicate that CSF-1 can signal to epithelial cells in the body by direct autocrine and paracrine actions.In Chapter 4, the precise contribution of macrophages, macrophage-derived IGF-1 and renal epithelial cells following CSF-1 therapy was therefore examined in vitro using co-culture assays with bone marrow-derived macrophages and the immortalised renal mouse cortical tubular cell line. While the findings from the functional assays did not provide further insight into the mechanisms underlying the renoprotective effects of CSF-1 therapy, they did support our hypothesis that CSF-1 regulates macrophage-derived IGF-1 production. However, additional mechanistic experiments in a variety of animal models of renal disease in combination with blocking antibodies are needed to fully elucidate the functional contribution of CSF-1 therapy. A better understanding of the role of macrophages and the factors that control their phenotype and function may ultimately lead to the development of therapies that attenuate acute renal disease and prevent the progression to chronic renal failure for patients with renal disease.