Nephron deficit and low podocyte density increase risk of albuminuria and glomerulosclerosis in a model of diabetes

Physiological Reports, Journal Year: 2023, Volume and Issue: 11(2)

Published: Jan. 1, 2023

Podocytes are terminally differentiated epithelial cells in glomeruli. Podocyte injury and loss features of many diseases leading to chronic kidney disease (CKD). The developmental origins health hypothesis propose an adverse intrauterine environment can lead CKD later life, especially when a second postnatal challenge is experienced. aim this study was examine whether suboptimal maternal would result reduced podocyte endowment, increasing susceptibility diabetes-induced renal injury. Female C57BL/6 mice were fed low protein diet (LPD) induce growth restriction or normal (NPD) from 3 weeks before mating until weaning (postnatal Day 21, P21) nephron endowment assessed one male female offspring per litter. Littermates administered streptozotocin vehicle at 6 age. Urinary albumin excretion, glomerular size, podometrics following 18 hyperglycemia. LPD restricted had lower number P21. However, by 24 the deficit no longer evident despite neither albuminuria nor glomerulosclerosis observed. unaffected hyperglycemia NPD offspring. Diabetes increased volume reducing density, with more pronounced effects diabetic developed mild demonstrating earlier onset. also pathology. These findings indicate that growth-restricted normalized susceptible alterations density rapid onset than

Language: Английский

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The ability of remaining glomerular podocytes to adapt to the loss of their neighbours decreases with age

Cell and Tissue Research, Journal Year: 2022, Volume and Issue: 388(2), P. 439 - 451

Published: March 15, 2022

Progressive podocyte loss is a feature of healthy ageing. While previous studies have reported age-related changes in number, density and size associations with proteinuria glomerulosclerosis, few examined how the response remaining podocytes to depletion age. Mild was induced PodCreiDTR mice aged 1, 6, 12 18 months via intraperitoneal administration diphtheria toxin. Control received vehicle. Podometrics, glomerular pathology were assessed, together expression p-rp-S6, phosphorylation target that represents activity mammalian rapamycin (mTOR). Podocyte number per glomerulus did not change control 18-month time period examined. However, at had largest lowest density. 6 resulted mild albuminuria but no whereas similar levels both glomerulosclerosis. Following months, p-rp-S6 positive increased significantly, this associated an adaptive increase volume. age, unable further elevate mTOR or undergo hypertrophic adaptation depletion, resulting marked pathology. These findings demonstrate importance mTORC1-mediated hypertrophy physiological (ageing) settings, highlighting functional limit reached under conditions.

Language: Английский

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Novel therapeutic perspectives for crescentic glomerulonephritis through targeting parietal epithelial cell activation and proliferation

Expert Opinion on Therapeutic Targets, Journal Year: 2023, Volume and Issue: 27(1), P. 55 - 69

Published: Jan. 2, 2023

Introduction Kidney injury is clinically classified as crescentic glomerulonephritis (CrGN) when ≥50% of the glomeruli in a biopsy sample contain lesions. However, current strategies, such systemic immunosuppressive therapy and plasmapheresis for CrGN, are partially effective, these drugs have considerable side effects. Hence, targeted to prevent glomerular crescent formation expansion remains an unmet clinical need.Areas covered Hyperproliferative parietal epithelial cells (PECs) main constituent with cell-tracing evidence. Crescents obstruct flow primary urine, pressure capillaries, degenerate affected nephrons. We reviewed markers PEC activation proliferation, potential therapeutic effects thrombin receptor inhibitors, how podocytes cross-talk PECs. These experiments may help identify early specific targets prevention treatment injury.Expert opinion Inhibiting proliferation CrGN can alleviate progression, which has been supported by preclinical studies evidence genetic deletion. Clarifying outcome transformation podocyte phenotype suppressing thrombin, receptors, hyperproliferation strategies will be research goals next ten years.

Language: Английский

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Aging-Related Functional and Structural Changes in Renal Tissues: Lesson from a Camel Model

Microscopy and Microanalysis, Journal Year: 2021, Volume and Issue: 27(3), P. 566 - 578

Published: March 10, 2021

Abstract

Language: Английский

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Potential renal stem/progenitor cells identified by in vivo lineage tracing

AJP Renal Physiology, Journal Year: 2022, Volume and Issue: 322(4), P. F379 - F391

Published: Feb. 1, 2022

Mammalian kidneys consist of more than 30 different types cells. A challenging task is to identify and characterize the stem/progenitor subpopulations that establish lineage relationships among these cellular elements during nephrogenesis in embryonic neonate tissue homeostasis and/or injury repair mature kidney. Moreover, potential clinical utility cells holds promise for development new regenerative medicine approaches treatment renal diseases. Stem are defined by unlimited self-renewal capacity pluripotentiality. Progenitor have pluripotentiality but no or limited potential. Cre-LoxP-based vivo genetic tracing a powerful tool their native environment. Hypothetically, this technique enables investigators accurately track progeny single cell group The Cre/LoxP system has been widely used uncover function genes various mammalian tissues through analyses. In review, we summarize recent advances characterization Cre drivers use identifying both developing mouse kidneys.

Language: Английский

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