Podocyte injury and its consequences

Kidney International, Год журнала: 2016, Номер 89(6), С. 1221 - 1230

Опубликована: Март 19, 2016

Podocytes maintain the glomerular filtration barrier, and stability of this barrier depends on their highly differentiated postmitotic phenotype, which also defines particular vulnerability glomerulus. Recent podocyte biology gene disruption studies in vivo indicate a causal relationship between abnormalities single molecules proteinuria glomerulosclerosis. live under various stresses pathological stimuli. They adapt to homeostasis, but excessive stress leads maladaptation with complex biological changes including loss integrity dysregulation cellular metabolism. Podocyte injury causes detachment from basement membrane. In addition "sick" podocytes detachment, our understanding responses following needs address pathways sclerosis. Studies have found variety dysfunction vivo, such as podocyte-endothelial cross talk activation podocyte-parietal cell interactions, all help us understand scenario its consequences. This review focuses aspects adaptive or maladaptive that lead major consequence,

Язык: Английский

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Autophagy in acute kidney injury

Kidney International, Год журнала: 2016, Номер 89(4), С. 779 - 791

Опубликована: Янв. 22, 2016

Язык: Английский

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Causes and pathogenesis of focal segmental glomerulosclerosis

Nature Reviews Nephrology, Год журнала: 2014, Номер 11(2), С. 76 - 87

Опубликована: Дек. 2, 2014

Язык: Английский

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Molecular mechanisms of renal aging

Kidney International, Год журнала: 2017, Номер 92(3), С. 569 - 579

Опубликована: Июль 18, 2017

Язык: Английский

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Glomerular Aging and Focal Global Glomerulosclerosis

Journal of the American Society of Nephrology, Год журнала: 2015, Номер 26(12), С. 3162 - 3178

Опубликована: Июнь 3, 2015

Kidney aging is associated with an increasing proportion of globally scarred glomeruli, decreasing renal function, and exponentially ESRD prevalence. In model systems, podocyte depletion causes glomerulosclerosis, suggesting age-associated glomerulosclerosis could be caused by a similar mechanism. We measured number, size, density, glomerular volume in 89 normal kidney samples from living deceased donors poles nephrectomies. Podocyte nuclear density decreased age due to combination number per glomerulus increased volume. Compensatory cell hypertrophy prevented change the tuft occupied podocytes. Young kidneys had high reserve (podocyte >300 106µm3), but 70–80 years age, average to, <100 106µm3, corresponding hypertrophy. older detachment rate (urine podocin mRNA-to-creatinine ratio) was higher than at younger ages podocytes were stressed (increased urine podocin-to-nephrin mRNA ratio). Moreover, kidneys, proteinaceous material accumulated Bowman space glomeruli low density. subset these mass events occurred association becoming binucleate (mitotic catastrophe) subsequent wrinkling capillaries, collapse, periglomerular fibrosis. young patients underlying diseases pathologic identified focal global glomerulosclerosis. reduction may therefore directly lead all progressive can considered superimposed accelerators this process.

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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The emergence of the glomerular parietal epithelial cell

Nature Reviews Nephrology, Год журнала: 2014, Номер 10(3), С. 158 - 173

Опубликована: Янв. 28, 2014

Язык: Английский

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The ageing kidney: Molecular mechanisms and clinical implications

Ageing Research Reviews, Год журнала: 2020, Номер 63, С. 101151 - 101151

Опубликована: Авг. 21, 2020

As human life expectancy keeps increasing, ageing populations present a growing challenge for clinical practices. Human is associated with molecular, structural, and functional changes in variety of organ systems, including the kidney. During process, kidney experiences progressive decline as well macroscopic microscopic histological alterations, which are accentuated by systemic comorbidities like hypertension diabetes mellitus, or preexisting underlying diseases. Although per se does not cause injury, physiologic normal processes likely to impair reparative capacity thus predispose older people acute disease, chronic disease other renal Mechanistically, cell senescence plays key role ageing, involving number cellular signaling mechanisms, many may be harnessed international targets slowing even reversing ageing. This review summarizes characteristics highlights latest progresses deciphering envisages potential interventional strategies novel therapeutic preventing improving hope maintaining long-term health function across course.

Язык: Английский

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Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis

Kidney International, Год журнала: 2015, Номер 88(5), С. 999 - 1012

Опубликована: Май 20, 2015

As adult podocytes cannot adequately proliferate following depletion in disease states, there has been interest the potential role of progenitors podocyte repair and regeneration. To determine whether parietal epithelial cells (PECs) can serve as disease-induced depletion, PECs were permanently labeled PEC-rtTA/LC1/R26 reporter mice. In normal mice, confined to Bowman's capsule, whereas (cytotoxic sheep anti-podocyte antibody) found glomerular tuft progressively higher numbers by days 7, 14, 28. Early disease, majority coexpressed CD44. By day 28, when significantly severity was lower, proteins but not Neither on nor stained for proliferation marker BrdU. The de novo expression phospho-ERK colocalized CD44 expressing PECs, markers. Thus, a mouse model focal segmental glomerulosclerosis typified abrupt followed regeneration, undergo two phenotypic changes once they migrate tuft. Initially these are predominantly activated coinciding with glomerulosclerosis, later exhibit phenotype, which is likely reparative.

Язык: Английский

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Podocyte Regeneration Driven by Renal Progenitors Determines Glomerular Disease Remission and Can Be Pharmacologically Enhanced

Stem Cell Reports, Год журнала: 2015, Номер 5(2), С. 248 - 263

Опубликована: Июль 30, 2015

Podocyte loss is a general mechanism of glomerular dysfunction that initiates and drives the progression chronic kidney disease, which affects 10% world population. Here, we evaluate whether regenerative response to podocyte injury influences disease outcome. In models focal segmental glomerulosclerosis performed in inducible transgenic mice where podocytes are tagged, remission or was determined by amount regenerated podocytes. When same model established renal progenitors remitted if successfully differentiated into podocytes, while it persisted differentiation ineffective, resulting glomerulosclerosis. Treatment with BIO, GSK3s inhibitor, significantly increased enhancing progenitor sensitivity effect endogenous retinoic acid. These results establish as critical determinants outcome pharmacological enhancement their possible therapeutic strategy.

Язык: Английский

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