A Review of Podocyte Biology

American Journal of Nephrology, Journal Year: 2018, Volume and Issue: 47(Suppl. 1), P. 3 - 13

Published: Jan. 1, 2018

Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked dysfunctions renal glomerulus involving function podocyte epithelial cells, including foot process effacement.Developments imaging technology are improving knowledge detailed structure human and cortex. processes attach themselves glomerular capillaries at basement membrane (GBM) forming intercellular junctions form slit diaphragm filtration barriers maintain normal function. Damage this area implicated disease. Injured podocytes undergo effacement whereby they lose their spread out, leading reduction barrier Effacement typically presence proteinuria focal segmental glomerulosclerosis, minimal change disease, diabetes. It thought be due breakdown actin cytoskeleton processes, complex contractile apparatuses allow dynamically reorganize according changes requirements. The depletion correlates development sclerosis chronic kidney Focal adhesion complexes interact underlying GBM bind within prevent detachment. Key Messages: Knowledge helping advance our mechanics filtering process, opening way variety new potential applications for clinical targeting.

Language: Английский

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Mechanisms of podocyte injury and implications for diabetic nephropathy

Clinical Science, Journal Year: 2022, Volume and Issue: 136(7), P. 493 - 520

Published: April 1, 2022

Abstract Albuminuria is the hallmark of both primary and secondary proteinuric glomerulopathies, including focal segmental glomerulosclerosis (FSGS), obesity-related nephropathy, diabetic nephropathy (DN). Moreover, albuminuria an important feature all chronic kidney diseases (CKDs). Podocytes play a key role in maintaining permselectivity glomerular filtration barrier (GFB) injury podocyte, leading to foot process (FP) effacement podocyte loss, unifying underlying mechanism glomerulopathies. The metabolic insult hyperglycemia paramount importance pathogenesis DN, while insults damage are poorly defined other However, shared mechanisms have been identified. Herein, we will review haemodynamic oxidative stress, inflammation, lipotoxicity, endocannabinoid (EC) hypertone, mitochondrial autophagic dysfunction damage, focussing particularly on their DN. Gaining better insight into may provide novel targets for treatment. strategies boosting repair open way regenerative medicine.

Language: Английский

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Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 19, 2024

Diabetic kidney disease (DKD) is a long-term and serious complication of diabetes that affects millions people worldwide. It characterized by proteinuria, glomerular damage, renal fibrosis, leading to end-stage disease, the pathogenesis complex involves multiple cellular molecular mechanisms. Among three kinds intraglomerular cells including podocytes, endothelial (GECs) mesangial (MCs), alterations in one cell type can produce changes others. The cell-to-cell crosstalk plays crucial role maintaining filtration barrier (GFB) homeostasis. In this review, we summarized recent advances understanding pathological interactions these types DKD then focused on signaling pathways factors mediate crosstalk, such as angiopoietins, vascular growth factors, transforming factor-β, Krüppel-like retinoic acid receptor response protein 1 exosomes, etc. Furthermore, also simply introduce application latest technologies studying within new promising mediators for DKD. conclusion, review provides comprehensive updated overview highlights its importance development novel intervention approaches.

Language: Английский

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Regulation of the Actin Cytoskeleton in Podocytes

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1700 - 1700

Published: July 16, 2020

Podocytes are an integral part of the glomerular filtration barrier, a structure that prevents large proteins and macromolecules into urine. Podocyte function is dependent on actin cytoskeleton regulation within foot processes, structures link podocytes to basement membrane. Actin dynamics in podocyte processes complex regulated by multiple other factors. There two key signal integration structural hubs regulate cytoskeleton: slit diaphragm focal adhesions. Both modulate filament extension as well process mobility. No matter what initial cause, final common pathway damage dysregulation leading retraction proteinuria. Disruption can be due acquired causes or genetic mutations regulatory signaling proteins. Here, we describe major components dysregulation.

Language: Английский

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Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11857 - 11857

Published: Nov. 1, 2021

Diabetic kidney disease (DKD) is the leading cause of chronic and end-stage renal disease. The natural history DKD includes glomerular hyperfiltration, progressive albuminuria, declining estimated filtration rate, and, ultimately, failure. It known that associated with metabolic changes caused by hyperglycemia, resulting in hypertrophy, glomerulosclerosis, tubulointerstitial inflammation fibrosis. Hyperglycemia also to programmed epigenetic modification. However, detailed mechanisms involved onset progression remain elusive. In this review, we discuss recent advances regarding pathogenic DKD.

Language: Английский

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Cell maturation: Hallmarks, triggers, and manipulation

Cell, Journal Year: 2022, Volume and Issue: 185(2), P. 235 - 249

Published: Jan. 1, 2022

Language: Английский

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High-resolution Slide-seqV2 spatial transcriptomics enables discovery of disease-specific cell neighborhoods and pathways

iScience, Journal Year: 2022, Volume and Issue: 25(4), P. 104097 - 104097

Published: March 16, 2022

High-resolution spatial transcriptomics enables mapping of RNA expression directly from intact tissue sections; however, its utility for the elucidation disease processes and therapeutically actionable pathways remains unexplored. We applied Slide-seqV2 to mouse human kidneys, in healthy distinct paradigms. First, we established feasibility nine which revealed a cell neighborhood centered around population

Language: Английский

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The Wnt Signaling Pathway in Diabetic Nephropathy

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 4, 2022

Diabetic nephropathy (DN) is a serious kidney-related complication of both type 1 and 2 diabetes mellitus (T1DM, T2DM) the second major cause end-stage kidney disease. DN can lead to hypertension, edema, proteinuria. In some cases, even progress failure, life-threatening condition. The precise etiology pathogenesis remain unknown, although multiple factors are believed be involved. main pathological manifestations include mesangial expansion, thickening glomerular basement membrane, podocyte injury. Eventually, these will glomerulosclerosis, thus affecting renal function. There an urgent need develop new strategies for prevention treatment DN. Existing evidence shows that Wnt signaling cascade plays key role in regulating development Previous studies focused on canonical pathway Subsequently, accumulated mechanism non-canonical indicated Wnt/Ca 2+ Wnt/PCP also have essential roles progression this review, we summarize specific mechanisms occurrence injury, cell fibrosis. Also, elucidate significance process DN, uncovered supporting critical development.

Language: Английский

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Epithelial–mesenchymal plasticity in kidney fibrosis

genesis, Journal Year: 2023, Volume and Issue: 62(1)

Published: June 22, 2023

Summary Epithelial–mesenchymal transition (EMT) is an important biological process contributing to kidney fibrosis and chronic disease. This characterized by decreased epithelial phenotypes/markers increased mesenchymal phenotypes/markers. Tubular cells (TECs) are commonly susceptible EMT various stimuli, for example, transforming growth factor‐β (TGF‐β), cellular communication network factor 2, angiotensin‐II, fibroblast factor‐2, oncostatin M, matrix metalloproteinase‐2, tissue plasminogen activator (t‐PA), plasmin, interleukin‐1β, reactive oxygen species. Similarly, glomerular podocytes can undergo via these stimuli high glucose condition in diabetic of TECs leads tubulointerstitial glomerulosclerosis, respectively. Signaling pathways involved EMT‐mediated diverse complex. TGF‐β1/Smad Wnt/β‐catenin the major venues triggering podocytes. These two thus serve as therapeutic targets against fibrosis. To date, a number inhibitors have been identified characterized. As expected, majority affect pathways. In addition fibrosis, EMT‐targeted antifibrotic expected be effective treatment other organs/tissues.

Language: Английский

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Alport Syndrome: Clinical Spectrum and Therapeutic Advances

Kidney Medicine, Journal Year: 2023, Volume and Issue: 5(5), P. 100631 - 100631

Published: March 21, 2023

Alport syndrome is a hereditary disorder characterized by kidney disease, ocular abnormalities, and sensorineural hearing loss. Work in understanding the cause of molecular composition glomerular basement membrane ultimately led to identification COL4A3, COL4A4 (both on chromosome 2q36), COL4A5 (chromosome Xq22), encoding α3, α4, α5 chains type IV collagen, as responsible genes. Subsequent studies suggested that autosomal recessive males with X-linked have more severe whereas dominant females variability. Variant also influential-protein-truncating variants or often present symptoms, failure, extrarenal manifestations, lack α3-α4-α5(IV) network. By contrast, mild-moderate forms from missense display are associated protracted involvement without manifestations. Regardless type, therapeutic intervention for focused early initiation angiotensin-converting enzyme inhibitors. There several therapies under investigation including sodium/glucose cotransporter 2 inhibitors, aminoglycoside analogs, endothelin A antagonists, lipid-modifying drugs, hydroxychloroquine, although targeting underlying defect through gene therapy remains preclinical stages.

Language: Английский

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