The Mechanism of Hyperglycemia-Induced Renal Cell Injury in Diabetic Nephropathy Disease: An Update

Life, Год журнала: 2023, Номер 13(2), С. 539 - 539

Опубликована: Фев. 15, 2023

Diabetic Nephropathy (DN) is a serious complication of type I and II diabetes. It develops from the initial microproteinuria to end-stage renal failure. The main initiator for DN chronic hyperglycemia. Hyperglycemia (HG) can stimulate resident non-resident cells produce humoral mediators cytokines that lead functional phenotypic changes in tissues, interference with cell growth, interacting proteins, advanced glycation end products (AGEs), etc., ultimately resulting glomerular tubular damage onset kidney disease. Therefore, poor blood glucose control particularly important risk factor development DN. In this paper, types mechanisms are classified summarized by reviewing related literature concerning effect hyperglycemia on At cellular level, we summarize effects This expected provide therapeutic ideas inspiration further studies treatment patients

Язык: Английский

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Unraveling the Role of Podocyte Turnover in Glomerular Aging and Injury

Journal of the American Society of Nephrology, Год журнала: 2014, Номер 25(4), С. 707 - 716

Опубликована: Янв. 10, 2014

Podocyte loss is a major determinant of progressive CKD. Although recent studies showed that subset parietal epithelial cells can serve as podocyte progenitors, the role turnover and regeneration in repair, aging, nephron remains unclear. Here, we combined genetic fate mapping with highly efficient isolation protocols to precisely quantify regeneration. We demonstrate give rise fully differentiated visceral indistinguishable from resident podocytes limited renewal occurs diphtheria toxin model acute ablation. In contrast, compensatory programs initiated response evoke glomerular hypertrophy, but not de novo generation. addition, no could be detected aging mice under physiologic conditions. absence replacement, characteristic features mouse kidneys included accumulation oxidized proteins, deposits protein aggregates, podocytes, glomerulosclerosis. summary, quantitative investigation vivo provides novel insights into mechanism capacity mice. Our data reveal generation mainly confined development may occur after injury, it fails regenerate or loss.

Язык: Английский

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Podocytes

F1000Research, Год журнала: 2016, Номер 5, С. 114 - 114

Опубликована: Янв. 28, 2016

Podocytes are highly specialized cells of the kidney glomerulus that wrap around capillaries and neighbor Bowman's capsule. When it comes to glomerular filtration, podocytes play an active role in preventing plasma proteins from entering urinary ultrafiltrate by providing a barrier comprising filtration slits between foot processes, which aggregate represent dynamic network cellular extensions. Foot processes interdigitate with adjacent form narrow rather uniform gaps. The fenestrated endothelial retain blood but permit passage small solutes overlying basement membrane less permeable macromolecules, particular albumin. cytoskeletal dynamics structural plasticity as well signaling each these distinct layers essential for efficient thus proper renal function. genetic or acquired impairment may lead process effacement (podocyte fusion retraction), morphological hallmark proteinuric diseases. Here, we briefly discuss aspects contemporary view patterns changes associated common diseases, current state basic clinical research.

Язык: Английский

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Divergent functions of the Rho GTPases Rac1 and Cdc42 in podocyte injury

Kidney International, Год журнала: 2013, Номер 84(5), С. 920 - 930

Опубликована: Май 15, 2013

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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Urine Podocyte mRNAs, Proteinuria, and Progression in Human Glomerular Diseases

Journal of the American Society of Nephrology, Год журнала: 2013, Номер 24(12), С. 2081 - 2095

Опубликована: Сен. 20, 2013

Model systems demonstrate that progression to ESRD is driven by progressive podocyte depletion (the hypothesis) and can be noninvasively monitored through measurement of urine pellet mRNAs. To test these concepts in humans, we analyzed mRNAs from 358 adult pediatric kidney clinic patients 291 controls (n=1143 samples). Compared with controls, increased 79-fold (P<0.001) biopsy-proven glomerular disease a 50% decrease function or ESRD. An independent cohort Alport syndrome had 23-fold increase urinary (P<0.001 compared controls). Urinary during active but returned baseline on remission. Furthermore, all categories evaluated, levels ranged high normal, consistent individual patient variability the risk for progression. In contrast, did not polycystic disease. The association between proteinuria podocyturia varied markedly type: correlation minimal-change low membranous nephropathy. These data support hypothesis as mechanism driving human diseases, suggest could useful monitoring response treatment, provide novel insights into pathophysiology.

Язык: Английский

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Estimating Podocyte Number and Density Using a Single Histologic Section

Journal of the American Society of Nephrology, Год журнала: 2013, Номер 25(5), С. 1118 - 1129

Опубликована: Дек. 20, 2013

The reduction in podocyte density to levels below a threshold value drives glomerulosclerosis and progression ESRD. However, technical demands prohibit high-throughput application of conventional morphometry for estimating density. We evaluated method using single paraffin-embedded formalin-fixed sections. Podocyte nuclei were imaged indirect immunofluorescence detection antibodies against Wilms' tumor-1 or transducin-like enhancer split 4. To account the large size relation section thickness, we derived correction factor given by equation CF=1/(D/T+1), where T is tissue thickness D mean caliper diameter nuclei. Normal values directly measured thick sections 3- 5-μm calibrated imaging software. larger human than rat mouse (P<0.01). In addition, did not vary significantly between kidney biopsies at time transplantation, 3-6 months after with depletion associated transplant glomerulopathy. models, also depletion, but increased approximately 10% old age postnephrectomy hypertrophy. A spreadsheet embedded formulas was created facilitate individualized estimation upon input values. validated comparison other methods, provided data comparable prior normal donors. This applicable laboratory clinical use.

Язык: Английский

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The metabolic syndrome and chronic kidney disease

Translational research, Год журнала: 2016, Номер 183, С. 14 - 25

Опубликована: Дек. 9, 2016

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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Nephrotoxic Effects of Common and Emerging Drugs of Abuse

Clinical Journal of the American Society of Nephrology, Год журнала: 2014, Номер 9(11), С. 1996 - 2005

Опубликована: Июль 18, 2014

The kidneys can be injured in diverse ways by many drugs, both legal and illegal. Novel associations descriptions of nephrotoxic effects common emerging drugs abuse have appeared over the past several years. Anabolic androgenic steroids, illicitly used athletes others for decades to increase muscle mass decrease body fat, are as podocyte toxins given recent severe forms FSGS long-term abusers. Synthetic cannabinoids, a new group compounds with marijuana-like effects, recently became popular recreational been associated an atypical form AKI. 3,4-Methylenedioxymethamphetamine, commonly known ecstasy, is widely synthetic drug mood-enhancing properties constellation toxicities that result death. These toxic include hyperthermia, hypotonic hyponatremia due its arginine vasopressin secretagogue-like rhabdomyolysis, cardiovascular collapse. Cocaine, serotonin-norepinephrine-dopamine reuptake inhibitor serves illegal stimulant, appetite suppressant, anesthetic, also causes vasoconstriction rhabdomyolysis. Recent adulteration much world's supply cocaine levamisole, antihelminthic agent attributes similar but distinct from those cocaine, appears spawned type ANCA-associated systemic vasculitis. This review discusses these abuse, which community health care providers should become aware their widespread abuse. Future investigation into pathogenetic mechanisms critical may provide window lessen even prevent perhaps allow deeper understanding nephrotoxicities themselves.

Язык: Английский

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