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Biomedicine & Pharmacotherapy =... Jun 2007Glomerular epithelial cell (podocyte) biology has been focused on in the last few years. The emerging understanding in podocyte biology has improved the molecular... (Review)
Review
Glomerular epithelial cell (podocyte) biology has been focused on in the last few years. The emerging understanding in podocyte biology has improved the molecular mechanism knowledge in many glomerular diseases. Urinary podocyte count and measurement of urinary podocyte specific markers (nephrin and podocalyxin) have been developed to detect podocyte injury. We discuss the emerging clinical importance of the urinary podocyte count in experimental and human glomerular disease, as well as measurement of urinary podocyte specific marker.
Topics: Animals; Biomarkers; Cell Count; Humans; Kidney Diseases; Membrane Proteins; Podocytes; Proteinuria; Urine
PubMed: 17532599
DOI: 10.1016/j.biopha.2006.12.009 -
Advances in Chronic Kidney Disease May 2017Podocytes form the visceral layer of a kidney glomerulus and express a characteristic octopus-like cellular architecture specialized for the ultrafiltration of blood.... (Review)
Review
Podocytes form the visceral layer of a kidney glomerulus and express a characteristic octopus-like cellular architecture specialized for the ultrafiltration of blood. The cytoskeletal dynamics and structural elasticity of podocytes rely on the self-organization of highly interconnected actin bundles, and the maintenance of these features is important for the intact glomerular filtration. Development of more differentiated podocytes in culture has dramatically increased our understanding of the molecular mechanisms regulating podocyte actin dynamics. Podocytes are damaged in a variety of kidney diseases, and therapies targeting podocytes are being investigated with increasing efforts. Association between podocyte damage and disease severity-or between podocyte recovery and the performance of therapeutic molecules-have been the venues of research for years. In this perspective, more standardized high--content screening has emerged as a powerful tool for visualization and analysis of podocyte morphology. This high-throughput fluorescence microscopy technique is based on an automated image analysis with simultaneous detection of various phenotypes (multiplexing) across multiple phenotypic parameters (multiparametric). Here, we review the principles of high-content screening technology and summarize efforts to carry out small compound screen using podocytes.
Topics: Actins; Cells, Cultured; Cytoskeleton; Humans; Image Processing, Computer-Assisted; Microscopy, Fluorescence; Phenotype; Podocytes
PubMed: 28501082
DOI: 10.1053/j.ackd.2017.04.001 -
Pflugers Archiv : European Journal of... Aug 2017In this article, I shall outline some of the most important aspects of the evidentiary basis of the so-called Kriz model for the development of glomerular sclerosis, a... (Review)
Review
In this article, I shall outline some of the most important aspects of the evidentiary basis of the so-called Kriz model for the development of glomerular sclerosis, a model that we continue to modify to this day. In my mind, the most important findings include the fact that podocytes are generally post-mitotic cells, so that loss of a significant number for any cause leads to podocyte insufficiency. Another pivotal finding is that in many experimental models and in human disease, podocytes detach from the GBM as living cells. These facts, together with biomechanical deduction, have led to the ongoing evolution of the original Heidelberg model.
Topics: Animals; Biomechanical Phenomena; Glomerulonephritis; Humans; Podocytes; Sclerosis; Stress, Mechanical
PubMed: 28643148
DOI: 10.1007/s00424-017-2012-0 -
American Journal of Physiology. Renal... Jun 2024Autophagy is a protective mechanism through which cells degrade and recycle proteins and organelles to maintain cellular homeostasis and integrity. An accumulating body... (Review)
Review
Autophagy is a protective mechanism through which cells degrade and recycle proteins and organelles to maintain cellular homeostasis and integrity. An accumulating body of evidence underscores the significant impact of dysregulated autophagy on podocyte injury in chronic kidney disease (CKD). In this review, we provide a comprehensive overview of the diverse types of autophagy and their regulation in cellular homeostasis, with a specific emphasis on podocytes. Furthermore, we discuss recent findings that focus on the functional role of different types of autophagy during podocyte injury in chronic kidney disease. The intricate interplay between different types of autophagy and podocyte health requires further research, which is critical for understanding the pathogenesis of CKD and developing targeted therapeutic interventions.
Topics: Podocytes; Autophagy; Humans; Renal Insufficiency, Chronic; Animals; Signal Transduction; Homeostasis
PubMed: 38601984
DOI: 10.1152/ajprenal.00415.2023 -
Nephron. Physiology 2009The kidney podocyte is a terminally differentiated and highly specialized cell. The function of the glomerular filtration barrier depends on the integrity of the... (Review)
Review
The kidney podocyte is a terminally differentiated and highly specialized cell. The function of the glomerular filtration barrier depends on the integrity of the podocyte. Podocyte injury and loss have been observed in human and experimental models of glomerular diseases. Three major podocyte phenotypes have been described in glomerular diseases: effacement, apoptosis, and proliferation. Here, we highlight the signaling cascades that are responsible for the manifestation of these pathologic phenotypes. The integrity of the podocyte foot process is determined by the interaction of nephrin with proteins in the slit diaphragm complex, the regulation of actin dynamics by the Rho family of GTPases, and the transduction of extracellular signals through focal adhesion complexes. Activation of the p38 mitogen-activated protein kinase and transforming growth factor-beta1 causes podocyte apoptosis. Phosphoinositide 3-kinase and its downstream target AKT protect podocytes from apoptosis. In human immunodeficiency virus-associated nephropathy, Src-dependent activation of Stat3, mitogen-activated protein kinase 1,2, and hypoxia-inducible factor 2alpha is an important driver of podocyte proliferation. At the level of intracellular signaling, it appears that different extracellular signals can converge onto a few pathways to induce changes in the phenotype of podocytes.
Topics: Animals; Apoptosis; Cell Dedifferentiation; Cell Proliferation; Cytoskeleton; Glomerular Basement Membrane; Humans; Intracellular Signaling Peptides and Proteins; Kidney Diseases; Phenotype; Podocytes; Signal Transduction
PubMed: 19142027
DOI: 10.1159/000191075 -
Clinical Journal of the American... Aug 2014
Topics: Cell Proliferation; Female; Humans; Kidney Diseases; Podocytes; Pre-Eclampsia; Pregnancy
PubMed: 25035271
DOI: 10.2215/CJN.05940614 -
Seminars in Nephrology Jul 2012Podocytes are highly specialized epithelial cells that line the urinary surface of the glomerular capillary tuft. To maintain kidney filtration, podocytes oppose the... (Review)
Review
Podocytes are highly specialized epithelial cells that line the urinary surface of the glomerular capillary tuft. To maintain kidney filtration, podocytes oppose the high intraglomerular hydrostatic pressure, form a molecular sieve, secrete soluble factors to regulate other glomerular cell types, and provide synthesis and maintenance of the glomerular basement membrane. Impairment of any of these functions after podocyte injury results in proteinuria and possibly renal failure. Loss of glomerular podocytes is a key feature for the progression of renal diseases, and detached podocytes can be retrieved in the urine of patients with progressive glomerular diseases. Thus, the concept of podocyte loss as a hallmark of progressive glomerular disease has been widely accepted. However, the nature of events that promote podocyte detachment and whether detachment is preceded by any kind of podocyte cell death, such as apoptosis, necroptosis, or necrosis, still remains unclear and is discussed in this review.
Topics: Animals; Apoptosis; Autophagy; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Proliferation; Glomerulosclerosis, Focal Segmental; Humans; Mitochondria; Necrosis; Podocytes; Signal Transduction
PubMed: 22958494
DOI: 10.1016/j.semnephrol.2012.06.011 -
Contributions To Nephrology 2013IgA nephropathy (IgAN) encompasses different pathological entities, all of which are characterized by the mesangial deposition of IgA. Aberrantly glycosylated IgA... (Review)
Review
IgA nephropathy (IgAN) encompasses different pathological entities, all of which are characterized by the mesangial deposition of IgA. Aberrantly glycosylated IgA molecules appear to play a major role in the pathogenesis of IgAN. Both genetic and environmental factors contribute to the formation of IgG antibodies that binds to aberrantly glycosylated IgA molecules and the glomerular deposition of circulating polymeric IgA complexes. Mesangial cells serve as primary glomerular cell type injured in IgAN with a variety of pathological changes leading to progressive renal dysfunction. Recent evidence suggests that indirect podocyte injury also contributes to glomerular damage observed in IgAN. These mechanisms were demonstrated in cultured podocytes exposed to mesangial cell-conditioned medium of human IgAN. Large-scale biopsy series of human kidneys also suggest that podocyte injury plays a role in IgAN. In this review, we discuss the recent advances that have helped elucidate the mechanisms of podocyte injury in IgAN and how these mechanisms correlate with clinically important outcomes in human studies.
Topics: Cell Communication; Complement Activation; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Mesangial Cells; Podocytes
PubMed: 23689566
DOI: 10.1159/000348461 -
Renal Failure Nov 2017Epithelial-mesenchymal transition (EMT) is a tightly regulated process by which epithelial cells lose their hallmark epithelial characteristics and gain the features of... (Review)
Review
Epithelial-mesenchymal transition (EMT) is a tightly regulated process by which epithelial cells lose their hallmark epithelial characteristics and gain the features of mesenchymal cells. For podocytes, expression of nephrin, podocin, P-cadherin, and ZO-1 is downregulated, the slit diaphragm (SD) will be altered, and the actin cytoskeleton will be rearranged. Diabetes, especially hyperglycemia, has been demonstrated to incite podocyte EMT through several molecular mechanisms such as TGF-β/Smad classic pathway, Wnt/β-catenin signaling pathway, Integrins/integrin-linked kinase (ILK) signaling pathway, MAPKs signaling pathway, Jagged/Notch signaling pathway, and NF-κB signaling pathway. As one of the most fundamental prerequisites to develop ground-breaking therapeutic options to prevent the development and progression of diabetic kidney disease (DKD), a comprehensive understanding of the molecular mechanisms involved in the pathogenesis of podocyte EMT is compulsory. Therefore, the purpose of this paper is to update the research progress of these underlying signaling pathways and expound the podocyte EMT-related DKDs.
Topics: Diabetic Nephropathies; Epithelial-Mesenchymal Transition; Humans; Hyperglycemia; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Podocytes; Signal Transduction; Tight Junction Proteins
PubMed: 28413908
DOI: 10.1080/0886022X.2017.1313164 -
Pediatric Nephrology (Berlin, Germany) Jun 2010Proteinuria is an early sign of kidney disease and has gained increasing attention over the past decade because of its close association with cardio-vascular and renal... (Review)
Review
Proteinuria is an early sign of kidney disease and has gained increasing attention over the past decade because of its close association with cardio-vascular and renal morbidity and mortality. Podocytes have emerged as the cell type that is critical in maintaining proper functioning of the kidney filter. A few genes have been identified that explain genetic glomerular failure and recent insights shed light on the pathogenesis of acquired proteinuric diseases. This review highlights the unique role of the cysteine protease cathepsin L as a regulatory rather than a digestive protease and its action on podocyte structure and function. We provide arguments why many glomerular diseases can be regarded as podocyte enzymatic disorders.
Topics: Animals; Cathepsin L; Humans; Kidney Diseases; Podocytes
PubMed: 20130922
DOI: 10.1007/s00467-009-1425-1