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Zhongguo Zhong Yao Za Zhi = Zhongguo... Jul 2016Podocyte injury is closely related to proteinuria in the progress of diabetic nephropathy(DN). The pathological characters of podocyte injury mainly refer to the change... (Review)
Review
Podocyte injury is closely related to proteinuria in the progress of diabetic nephropathy(DN). The pathological characters of podocyte injury mainly refer to the change of podocyte form and function, including foot process effacement, reduction of podocyte number and density, podocyte apoptosis, podocyte epithelial-mesenchymal transdifferentiation(EMT)and podocyte hypertrophy. These pathological damages are controlled by multiple signaling pathways in the kidney, such as mammalian target of rapamycin(mTOR)/autophagy pathway, transforming growth factor(TGF)-β1 pathway and Notch pathway. For podocyte injuries induced by high glucose or in murine models of DN, some Chinese herbal medicine(CHM)extracts, such as multiglycoside of Tripterygium wilfordii(GTW), triptolide(TP), astragaloside IV(AS-IV), astragalus polysaccharide(APS)and Panax notoginseng saponins(PNS), have the protective effects in vivo or in vitro. The preliminary studies in China showed that GTW improves podocyte injury in the DN model rats probably through regulating the activity of mTORC1 signaling pathway in the kidney. Therefore, it is the developmental direction for the further study to clarify the interventional effects of CHM based on podocyte injury-related signaling pathway in DN.
Topics: Animals; Cell Transdifferentiation; China; Diabetic Nephropathies; Drugs, Chinese Herbal; Mice; Podocytes; Rats
PubMed: 28905562
DOI: 10.4268/cjcmm20161308 -
Current Pharmaceutical Design 2007Over the last five years, much work has underlined the important role of the podocyte in the development of diabetic nephropathy. The metabolic and haemodynamic... (Review)
Review
Over the last five years, much work has underlined the important role of the podocyte in the development of diabetic nephropathy. The metabolic and haemodynamic abnormalities of the diabetic milieu act in concert, perhaps via the common effector path of oxidative stress and development of reactive oxygen species, to promote podocyte damage. There is loss of nephrin from the slit diaphragm, increased synthesis of some of the components of the glomerular basement membrane, activation of pro-apoptotic and hypertrophic pathways, loss of the alpha3beta1 integrin and increased secretion of VEGF. These changes interact to lead to increased permeability, accumulation of abnormal extracellular matrix, apoptosis, foot process detachment and podocyte loss. The foot processes of the remaining podocytes hypertrophy and widen, with reduced filtration slit width. The end result is increasing proteinuria, basement membrane thickening and accumulation of mesangial matrix and declining renal function. Some currently used therapies, such as tight glucose control and inhibition of the renin angiotensin system, ameliorate these changes and prevent podocyte loss. Statins may also have a specific podocyte protective role. Other potential therapies include inhibitors of glycation, antioxidants, and inhibitors of growth factor and signalling pathways.
Topics: Animals; Diabetic Nephropathies; Drug Delivery Systems; Humans; Metabolic Networks and Pathways; Podocytes
PubMed: 17897015
DOI: 10.2174/138161207781662957 -
Kidney & Blood Pressure Research 2015The glomerular podocyte is exposed to numerous mechanical forces as a constituent of the glomerular filtration apparatus. This includes fluid shear stress (FSS)... (Review)
Review
The glomerular podocyte is exposed to numerous mechanical forces as a constituent of the glomerular filtration apparatus. This includes fluid shear stress (FSS) displaced upon the podocytic foot process's apical, lateral, and basal surfaces. Even in the face of continuous flow the podocyte is capable of contributing to physiologic filtration, however with pathologic levels of hyperfiltration there is increased FSS placed upon the cell. The mechanisms by which the podocyte detects and responds to FSS are topics of recent investigations, with the aim to clarify the way these cells are injured and/or adapt in times of hyperfiltration and disease states. As the pathogenesis of numerous glomerulopathies is contingent on the status of the podocyte, understanding the manner that these cells can be modified by FSS is essential. Likewise, determination of the effect of such mechanical forces upon other resident cells of the renal corpuscle would reveal the contribution of FSS in the progression of glomerular diseases. The biochemical manner in which podocytes sense and respond to FSS, that is mechanotransduction, will be discussed.
Topics: Animals; Glomerular Filtration Barrier; Humans; Kidney Glomerulus; Mechanotransduction, Cellular; Podocytes; Rheology
PubMed: 25871438
DOI: 10.1159/000368493 -
Nihon Rinsho Men'eki Gakkai Kaishi =... 2011Podocytes are glomerular visceral epithelial cells, which function as molecular sieve with foot process (FT) and slit diaphragm (SD) spanning FT, not to allow high... (Review)
Review
Podocytes are glomerular visceral epithelial cells, which function as molecular sieve with foot process (FT) and slit diaphragm (SD) spanning FT, not to allow high molecular weight protein to be filtrated through glomerular capillary loop. Pathological proteinuria is caused by discoordinated tertiary podocyte structure such as disappearance of FT and/or SD, and irreversible glomeular sclerosis is caused by podocyte loss due to cell death and/or detachment from capillary wall. With recent advance of nephrological research technology such as podocyte cell culture system, genetically engineered transgenic mice with podocyte-specific regulation of gene expression, podocyte-associated biomarkers, the new isolation method of glomeruli, laser capture microdissection, multiphoton imaging and extracellular flux analyzer, new findings of pathogenesis of glomerular lesions will be expected, not only in primary glomerulonephritis, but also in secondary glomerulonephritis or glomerulopathy due to rheumatic diseases.
Topics: Animals; Apoptosis; Biomarkers; Humans; Podocytes; Rheumatic Diseases
PubMed: 21372512
DOI: 10.2177/jsci.34.40 -
The International Journal of... Sep 2010In the past decade, podocyte research has been greatly aided by the development of powerful new molecular, cellular and animal tools, leading to elucidation of an... (Review)
Review
In the past decade, podocyte research has been greatly aided by the development of powerful new molecular, cellular and animal tools, leading to elucidation of an increasing number of proteins involved in podocyte function and identification of mutated genes in hereditary glomerulopathies. Accumulating evidence indicates that podocyte disorders may not only underlie these hereditary glomerulopathies but also play crucial role in a broad spectrum of acquired glomerular diseases. Genetic susceptibility, environmental influence and systemic responses are all involved in the mediation of the pathogenesis of podocytopathies. Injured podocytes may predisopose to further injury of other podocytes and other adjacent/distant renal cells in a vicious cycle, leading to inexorable progression of glomerular injury. The classic view is that podocytes have a limited ability to proliferate in the normal mature kidney. However, recent research in rodents has provided suggestive evidence for podocyte regeneration resulting from differentiation of progenitor cells within Bowman's capsule.
Topics: Animals; Bowman Capsule; Cell Differentiation; Humans; Kidney; Kidney Glomerulus; Podocytes; Stem Cells
PubMed: 20542138
DOI: 10.1016/j.biocel.2010.05.014 -
Seminars in Nephrology Jul 2012Renal fibrosis is the major determinant in progression of acute and chronic kidney diseases. Transforming growth factor-β (TGF-β) has been shown to be an important... (Review)
Review
Renal fibrosis is the major determinant in progression of acute and chronic kidney diseases. Transforming growth factor-β (TGF-β) has been shown to be an important mediator of progressive fibrosis. Several studies have implicated that TGF-β1 is involved in the tight balance of survival and apoptotic responses in podocytes that are Smad-dependent or independent. Bone morphogenic protein-7 (BMP-7), another member of the TGF-β superfamily, has to date been involved primarily in kidney development and was described as an active blocker of TGF-β-induced profibrotic effects. Here, we summarize the direct effects of these two cytokines on podocytes. We describe their involvement in podocyte survival and apoptosis pathways with the potential to modify the critical steps in podocyte apoptosis induction. Our group has analyzed the cross-talk of BMP-7 and TGF-β1 signaling in podocytes and we describe BMP-7 as a cytoprotective factor that could antagonize proapoptotic TGF-β signals. In addition, we identified various extracellular and intracellular modifiers that can influence this sensitive cross-talk. On the basis of our work and the work of others we conclude that the balance of TGF-β1 and BMP-7 signaling and involvement of extracellular and intracellular modifiers in these cascades are important parts of podocyte physiology and pathophysiology.
Topics: Animals; Apoptosis; Bone Morphogenetic Protein 7; Cell Survival; Humans; Insulin-Like Growth Factor Binding Protein 3; MAP Kinase Signaling System; Podocytes; Signal Transduction; Smad Proteins; Transforming Growth Factor beta
PubMed: 22958491
DOI: 10.1016/j.semnephrol.2012.06.008 -
The American Journal of Pathology Nov 2013Podocytes represent an essential component of the kidney's glomerular filtration barrier. They stay attached to the glomerular basement membrane via integrin... (Review)
Review
Podocytes represent an essential component of the kidney's glomerular filtration barrier. They stay attached to the glomerular basement membrane via integrin interactions that support the capillary wall to withstand the pulsating filtration pressure. Podocyte structure is maintained by a dynamic actin cytoskeleton. Terminal differentiation is coupled with permanent exit from the cell cycle and arrest in a postmitotic state. Postmitotic podocytes do not have an infinite life span; in fact, physiologic loss in the urine is documented. Proteinuria and other injuries accelerate podocyte loss or induce death. Mature podocytes are unable to replicate and maintain their actin cytoskeleton simultaneously. By the end of mitosis, cytoskeletal actin forms part of the contractile ring, rendering a round shape to podocytes. Therefore, when podocyte mitosis is attempted, it may lead to aberrant mitosis (ie, mitotic catastrophe). Mitotic catastrophe implies that mitotic podocytes eventually detach or die; this is a previously unrecognized form of podocyte loss and a compensatory mechanism for podocyte hypertrophy that relies on post-G1-phase cell cycle arrest. In contrast, local podocyte progenitors (parietal epithelial cells) exhibit a simple actin cytoskeleton structure and can easily undergo mitosis, supporting podocyte regeneration. In this review we provide an appraisal of the in situ pathology of mitotic catastrophe compared with other proposed types of podocyte death and put experimental and renal biopsy data in a unified perspective.
Topics: Animals; Cell Death; HIV Infections; Humans; Hypertrophy; Kidney Diseases; Mitosis; Podocytes
PubMed: 24007883
DOI: 10.1016/j.ajpath.2013.06.033 -
American Journal of Physiology. Renal... Feb 2013Progressive loss of podocytes is the most frequent cause accounting for end-stage renal failure. Podocytes are complex, terminally differentiated cells incapable of... (Review)
Review
Progressive loss of podocytes is the most frequent cause accounting for end-stage renal failure. Podocytes are complex, terminally differentiated cells incapable of replicating. Thus lost podocytes cannot be replaced by proliferation of neighboring undamaged cells. Moreover, podocytes occupy a unique position as epithelial cells, adhering to the glomerular basement membrane (GBM) only by their processes, whereas their cell bodies float within the filtrate in Bowman's space. This exposes podocytes to the danger of being lost by detachment as viable cells from the GBM. Indeed, podocytes are continually excreted as viable cells in the urine, and the rate of excretion dramatically increases in glomerular diseases. Given this situation, it is likely that evolution has developed particular mechanisms whereby podocytes resist cell detachment. Podocytes respond to stress and injury by undergoing tremendous changes in shape. Foot process effacement is the most prominent and, yet in some ways, the most enigmatic of those changes. This review summarizes the various structural responses of podocytes to injury, focusing on foot process effacement and detachment. We raise the hypothesis that foot process effacement represents a protective response of podocytes to escape detachment from the GBM.
Topics: Animals; Bowman Capsule; Glomerular Basement Membrane; Humans; Kidney Diseases; Mice; Podocytes; Rats; Stress, Physiological
PubMed: 23235479
DOI: 10.1152/ajprenal.00478.2012 -
American Journal of Physiology. Renal... Dec 2020Mitochondria play a complex role in maintaining cellular function including ATP generation, generation of biosynthetic precursors for macromolecules, maintenance of...
Mitochondria play a complex role in maintaining cellular function including ATP generation, generation of biosynthetic precursors for macromolecules, maintenance of redox homeostasis, and metabolic waste management. Although the contribution of mitochondrial function in various kidney diseases has been studied, there are still avenues that need to be explored under healthy and diseased conditions. Mitochondrial damage and dysfunction have been implicated in experimental models of podocytopathy as well as in humans with glomerular diseases resulting from podocyte dysfunction. Specifically, in the podocyte, metabolism is largely driven by oxidative phosphorylation or glycolysis depending on the metabolic needs. These metabolic needs may change drastically in the presence of podocyte injury in glomerular diseases such as diabetic kidney disease or focal segmental glomerulosclerosis. Here, we review the role of mitochondria in the podocyte and the factors regulating its function at baseline and in a variety of podocytopathies to identify potential targets for therapy.
Topics: Humans; Kidney Diseases; Mitochondria; Podocytes
PubMed: 33073585
DOI: 10.1152/ajprenal.00393.2020 -
Seminars in Nephrology Jul 2012Observations of hereditary glomerular disease support the contention that podocyte intercellular junction proteins are essential for junction formation and maintenance.... (Review)
Review
Observations of hereditary glomerular disease support the contention that podocyte intercellular junction proteins are essential for junction formation and maintenance. Genetic deletion of most of these podocyte intercellular junction proteins results in foot process effacement and proteinuria. This review focuses on the current understanding of molecular mechanisms by which podocyte intercellular junction proteins such as the nephrin-neph1-podocin-receptor complex coordinate cytoskeletal dynamics and thus intercellular junction formation, maintenance, and injury-dependent remodeling.
Topics: Actin Cytoskeleton; Animals; Humans; Intercellular Junctions; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Podocytes; Signal Transduction
PubMed: 22958485
DOI: 10.1016/j.semnephrol.2012.06.002