Cellular phenotypic transitions in diabetic nephropathy: An update

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 2, 2022

Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetes the most common end stage renal disease (ESRD). Renal fibrosis final pathological change DN. It widely believed that cellular phenotypic switching diabetic nephropathy. Several types kidney cells undergo activation differentiation become reprogrammed to express markers mesenchymal or podocyte-like cells. However, development targeted therapy for DN has not yet been identified. Here, we discussed pathophysiologic changes delineated possible origins contribute myofibroblasts podocytes through transitions. We also highlight molecular signaling pathways involved transition, which would provide valuable information designing effective therapies

Язык: Английский

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Podocyte Senescence and Aging

Kidney360, Год журнала: 2023, Номер 4(12), С. 1784 - 1793

Опубликована: Окт. 31, 2023

As the population in many industrial countries is aging, risk, incidence, and prevalence of CKD increases. In kidney, advancing age results a progressive decrease nephron number an increase glomerulosclerosis. this review, we focus on effect aging glomerular podocytes, post-mitotic epithelial cells critical for normal integrity function filtration barrier. The podocytes undergo senescence transition to senescence-associated secretory phenotype typified by production secretion inflammatory cytokines that can influence neighboring paracrine signaling. addition senescence, podocyte characterized ultrastructural functional changes; hypertrophy; cellular, oxidative, endoplasmic reticulum stress; reduced autophagy; increased expression genes. This health span shortened life span. Importantly, these changes pathways/processes characteristic healthy are also often similar pathways disease-induced injured podocyte. Finally, better understanding opens therapeutic options slow rate promote kidney health.

Язык: Английский

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Single-cell lineage tracing approaches to track kidney cell development and maintenance

Kidney International, Год журнала: 2024, Номер 105(6), С. 1186 - 1199

Опубликована: Март 28, 2024

Язык: Английский

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Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish

Journal of Developmental Biology, Год журнала: 2023, Номер 11(1), С. 9 - 9

Опубликована: Фев. 20, 2023

Podocytes are exquisitely fashioned kidney cells that serve an essential role in the process of blood filtration. Congenital malformation or damage to podocytes has dire consequences and initiates a cascade pathological changes leading renal disease states known as podocytopathies. In addition, animal models have been integral discovering molecular pathways direct development podocytes. this review, we explore how researchers used zebrafish illuminate new insights about processes podocyte ontogeny, model podocytopathies, create opportunities discover future therapies.

Язык: Английский

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Parietal Epithelial Cell Behavior and Its Modulation by microRNA-193a

Biomolecules, Год журнала: 2023, Номер 13(2), С. 266 - 266

Опубликована: Янв. 31, 2023

Glomerular parietal epithelial cells (PECs) have been increasingly recognized to crucial functions. Lineage tracking in animal models showed the expression of a podocyte phenotype by PECs during normal glomerular growth and after acute injury, suggesting reparative role PECs. Conversely, activated are speculated be pathogenic comprise extracapillary proliferation focal segmental glomerulosclerosis (FSGS) crescentic glomerulonephritis (CrescGN). The roles seem represent two sides PEC behavior directed local milieu mediators. Recent studies suggest microRNA-193a (miR193a) is involved pathogenesis FSGS CrescGN. In mouse model primary FSGS, induction miR193a caused downregulation Wilms' tumor protein, leading dedifferentiation podocytes. On other hand, inhibition resulted reduced crescent lesions Interestingly, vitro report that induces trans-differentiation into phenotype. This narrative review highlights critical health disease its modulation miR193a.

Язык: Английский

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Molecular Mechanisms of Renal Progenitor Regulation: How Many Pieces in the Puzzle?

Cells, Год журнала: 2021, Номер 10(1), С. 59 - 59

Опубликована: Янв. 2, 2021

Kidneys of mice, rats and humans possess progenitors that maintain daily homeostasis take part in endogenous regenerative processes following injury, owing to their capacity proliferate differentiate. In the glomerular tubular compartments nephron, consistent studies demonstrated well-characterized, distinct populations progenitor cells, localized parietal epithelium Bowman capsule scattered proximal distal tubules, could generate segment-specific cells physiological conditions tissue injury. However, defective or abnormal responses these can contribute pathologic conditions. The molecular characteristics renal have been extensively studied, revealing numerous classical evolutionarily conserved pathways, such as Notch Wnt/β-catenin, play a major role cell regulation. Others, retinoic acid, renin-angiotensin-aldosterone system, TLR2 (Toll-like receptor 2) leptin, are also important this process. review, we summarize plethora mechanisms directing during kidney Finally, will explore how single-cell RNA sequencing bring characterization next level, while knowing signature is gaining relevance clinic.

Язык: Английский

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The Pathology Lesion Patterns of Podocytopathies: How and why?

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Фев. 24, 2022

Podocytopathies are a group of proteinuric glomerular disorders driven by primary podocyte injury that associated with set lesion patterns observed on kidney biopsy, i.e., minimal changes, focal segmental glomerulosclerosis, diffuse mesangial sclerosis and collapsing glomerulopathy. These unspecific have long been considered as independent disease entities. By contrast, recent evidence from genetics experimental studies demonstrated they represent signs repeated repair attempts. ongoing processes depend the type, length, severity injury, well ability parietal epithelial cells to drive repair. In this review, we discuss main pathology podocytopathies focus cellular molecular response podocytes cells.

Язык: Английский

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

Physiological Reports, Год журнала: 2023, Номер 11(2)

Опубликована: Янв. 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

Язык: Английский

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Podocyte injury at young age causes premature senescence and worsens glomerular aging

AJP Renal Physiology, Год журнала: 2023, Номер 326(1), С. F120 - F134

Опубликована: Окт. 19, 2023

Glomerular function is decreased by aging. However, little known about the molecular mechanisms involved in age-related glomerular changes and which factors could contribute to a worse aging process. Here, we reported that podocyte injury young mice culture podocytes induced senescence, marker of aging, accelerates when compared with healthy mice.

Язык: Английский

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The recruitment mechanisms and potential therapeutic targets of podocytes from parietal epithelial cells

Journal of Translational Medicine, Год журнала: 2021, Номер 19(1)

Опубликована: Окт. 21, 2021

Abstract Podocytes are differentiated postmitotic cells which cannot be replaced after podocyte injury. The mechanism of repopulation injury has aroused wide concern. Parietal epithelial (PECs) heterogeneous and only a specific subpopulation PECs the capacity to replace podocytes. Major progress been achieved in recent years regarding role function subset could transdifferentiate toward Additionally, several factors, such as Notch, Wnt/ß-catenin, Wilms’ tumor-1, miR-193a growth arrest-specific protein 1, have shown involved these processes. Finally, serve potential therapeutic target conditions loss. In this review, we discuss latest observations concepts about recruitment podocytes from glomerular diseases well newly identified mechanisms most treatments for process.

Язык: Английский

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