Podocyte–actin dynamics in health and disease

Nature Reviews Nephrology, Год журнала: 2016, Номер 12(11), С. 692 - 710

Опубликована: Авг. 30, 2016

Язык: Английский

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Consequences of Glomerular Hyperfiltration: The Role of Physical Forces in the Pathogenesis of Chronic Kidney Disease in Diabetes and Obesity

˜The œNephron journals/Nephron journals, Год журнала: 2019, Номер 143(1), С. 38 - 42

Опубликована: Янв. 1, 2019

<b><i>Background:</i></b> Glomerular hyperfiltration (GH) is a hallmark of renal dysfunction in diabetes and obesity. Recent clinical trials demonstrated that SGLT2 inhibitors are renoprotective, possibly by abating hyperfiltration. The present review considers the current evidence for cause-to-effect relationship between hyperfiltration-related physical forces development chronic kidney disease (CKD). <b><i>Summary:</i></b> associated with glomerular tubular hypertrophy. Hyperfiltration mainly due to an increase capillary pressure, which increases tensile stress applied wall structures. In addition, increased ultrafiltrate flow into Bowman’s space heightens shear on podocyte foot processes body surface. These mechanical stresses lead basement membrane (GBM) length ability grow being limited, mismatch develops GBM area covered processes, leading injury, detachment viable podocytes, adherence capillaries parietal epithelium, synechia formation segmental sclerosis. Mechanical also post-filtration structures, resulting dilation urinary spaces, proximal sodium reabsorption hypertrophied epithelial cells activation mediators tubulointerstitial inflammation, hypoxia fibrosis <b><i>Key Messages:</i></b> GH-related leads both adaptive maladaptive changes. flow-related effects play central role pathogenesis disease. Attenuation thus important therapeutic target obesity-induced CKD.

Язык: Английский

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Mechanisms of podocyte injury and implications for diabetic nephropathy

Clinical Science, Год журнала: 2022, Номер 136(7), С. 493 - 520

Опубликована: Апрель 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.

Язык: Английский

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Role of biophysics and mechanobiology in podocyte physiology

Nature Reviews Nephrology, Год журнала: 2024, Номер 20(6), С. 371 - 385

Опубликована: Март 5, 2024

Язык: Английский

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Chronic kidney disease

Nature Reviews Disease Primers, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 30, 2025

Язык: Английский

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A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models

Science, Год журнала: 2017, Номер 358(6368), С. 1332 - 1336

Опубликована: Дек. 7, 2017

Progressive kidney diseases are often associated with scarring of the kidney's filtration unit, a condition called focal segmental glomerulosclerosis (FSGS). This is due to loss podocytes, cells critical for glomerular filtration, and leads proteinuria failure. Inherited forms FSGS caused by Rac1-activating mutations, Rac1 induces TRPC5 ion channel activity cytoskeletal remodeling in podocytes. Whether mediates onset progression unknown. We identified small molecule, AC1903, that specifically blocks glomeruli proteinuric rats. Chronic administration AC1903 suppressed severe prevented podocyte transgenic rat model FSGS. also provided therapeutic benefit hypertensive disease. These data indicate drives disease inhibitors may be valuable treatment progressive diseases.

Язык: Английский

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Nephrin Signaling in the Podocyte: An Updated View of Signal Regulation at the Slit Diaphragm and Beyond

Frontiers in Endocrinology, Год журнала: 2018, Номер 9

Опубликована: Июнь 5, 2018

Podocytes are a major component of the glomerular blood filtration barrier, and alterations to morphology their unique actin-based foot processes common feature kidney disease. Adjacent connected by specialized intercellular junction known as slit diaphragm (SD), which serves ultimate barrier regulate passage macromolecules from blood. While link between SD dysfunction reduced selectivity has been recognized for nearly 50 years, our understanding underlying molecular circuitry began only 20 years ago, sparked identification NPHS1, encoding transmembrane protein nephrin. Nephrin not functions core extracellular network, but also signaling scaffold via interactions at its short intracellular region. Phospho-regulation several conserved tyrosine residues in this region influences signal transduction pathways control podocyte cell adhesion, shape survival, emerging studies highlight roles nephrin phospho-dynamics mechanotransduction endocytosis. The following review aims summarize last 5 advancement knowledge how centered directs formation function. We further provide insight on promising frontiers biology, have implications healthy diseased kidney.

Язык: Английский

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Hypertensive nephropathy. Moving from classic to emerging pathogenetic mechanisms

Journal of Hypertension, Год журнала: 2016, Номер 35(2), С. 205 - 212

Опубликована: Окт. 26, 2016

Hypertensive kidney disease classically entails nephroangiosclerosis and hyalinosis with glomerular damage. However, in recent years, several evidences showed that high blood pressure also injures tubular cells, inducing epithelial-to-mesenchymal transition tubulointerstitial fibrosis. Recently investigated mechanisms are podocyte effacement loss, which lead to denudation of the basement membrane focal adhesion tufts Bowman's capsule, reduced filtration scars. Starting from classic concept nephroangiosclerosis, this review examines recently emerged knowledge new biochemical molecular underlying damage hypertension discusses how viable podocytes or podocyte-deriving proteins promising tools for early diagnosis renal remodelling hypertension.

Язык: Английский

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Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective

˜The œNephron journals/Nephron journals, Год журнала: 2020, Номер 144(9), С. 413 - 427

Опубликована: Янв. 1, 2020

Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular injury, rather than single disease, that caused by diverse clinicopathological entities with different mechanisms injury the podocyte as principal target lesion, leading to characteristic sclerotic lesions in parts (i.e., focal) some segmental) glomeruli. The lesion FSGS has shown an increasing prevalence over past few decades and considered most common cause ESKD. Primary FSGS, which usually presents nephrotic syndrome, thought be circulating permeability factors have main role foot process effacement. Secondary forms include maladaptive secondary hyperfiltration such obesity or cases loss nephron mass, virus-associated drug-associated can result direct injury. Genetic increasingly been recognized careful evaluation patients atypical primary should performed exclude genetic causes. Unlike do not respond immunosuppression tend recur after kidney transplantation. Distinguishing from causes prognostic significance crucial for appropriate management. In this review, we examine pathogenesis, clinical approach distinguish between causes, current recommendations management FSGS.

Язык: Английский

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Regulation of the Actin Cytoskeleton in Podocytes

Cells, Год журнала: 2020, Номер 9(7), С. 1700 - 1700

Опубликована: Июль 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.

Язык: Английский

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