Cell biology of diabetic nephropathy: Roles of endothelial cells, tubulointerstitial cells and podocytes

Maezawa, Yoshiro; Takemoto, Minoru; Yokote, Koutaro

doi:10.1111/jdi.12255

Cited by 165 publications

(141 citation statements)

References 149 publications

(190 reference statements)

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“…While the glomerulus is widely recognized as the primary site of injury in DN, tubular injury is also prominent. Tubular hypertrophy and interstitial inflammation are seen early in the course of DN [4–6] and with disease progression tubular atrophy and interstitial fibrosis develop in concert with declining renal function [5,7]. Cross-talk between podocytes and the tubular epithelium is believed to play an important role in the development of tubulointerstitial fibrosis and renal functional decline; however, the mechanisms by which this occurs are not fully understood [8–10].…”

Section: Introductionmentioning

confidence: 99%

Podocyte‐derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

Munkonda

Akbari

Landry

et al. 2018

J of Extracellular Vesicle

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Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100–1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses. MPs were isolated from the media of differentiated, untreated human podocytes (hPODs) and administered to cultured human proximal tubule epithelial cells (PTECs). Treatment with podocyte MPs increased p38 and Smad3 phosphorylation and expression of the extracellular matrix (ECM) proteins fibronectin and collagen type IV. MP-induced responses were attenuated by co-treatment with the p38 inhibitor SB202190. A transforming growth factor beta (TGF-β) receptor inhibitor (LY2109761) blocked MP-induced Smad3 phosphorylation and ECM protein expression but not p38 phosphorylation suggesting that these responses occurred downstream of p38. Finally, blockade of the class B scavenger receptor CD36 completely abrogated MP-mediated p38 phosphorylation, downstream Smad3 activation and fibronectin/collagen type IV induction. Taken together our results suggest that podocyte MPs interact with proximal tubule cells and induce pro-fibrotic responses. Such interactions may contribute to the development of tubular fibrosis in glomerular disease.

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Section: Introductionmentioning

confidence: 99%

Podocyte‐derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

Munkonda

Akbari

Landry

et al. 2018

J of Extracellular Vesicle

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“…The glomerular filtration barrier is a composite multilayered structure, and injury in one layer may spread to others and affect the whole function of the barrier [27]. It is well documented that endothelial glycocalyx plays a significant role in the glomerular filtration barrier [27,28].…”

mentioning

confidence: 99%

“…It is well documented that endothelial glycocalyx plays a significant role in the glomerular filtration barrier [27,28]. Dysfunction of the endothelial TJ is a crucial step in the development of endothelial hyperpermeability that contributes to progressive DN [5].…”

mentioning

confidence: 99%

Rutin Prevents High Glucose-Induced Renal Glomerular Endothelial Hyperpermeability by Inhibiting the ROS/Rhoa/ROCK Signaling Pathway

et al. 2016

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Diabetic nephropathy is a progressive kidney disease caused by damage to the capillaries in the glomeruli. Endothelial dysfunction is an early sign of diabetic cardiovascular disease and may contribute to progressive diabetic nephropathy. Hyperglycemia-induced endothelial hyperpermeability is crucial to diabetic nephropathy. Rutin has beneficial effects on diabetic nephropathy, but the exact mechanisms of its protective effect remain elusive. The aim of this study was to assess the role of pretreatment with rutin in an in vitro model of hyperglycemia-induced barrier dysfunction in human renal glomerular endothelial cells. Human renal glomerular endothelial cells were exposed to rutin and/or hyperglycemia for 24?h. Hyperglycemia increased permeability and decreased the junction protein occludin in the cell-cell junction area and the total expression in human renal glomerular endothelial cells, whereas rutin treatment significantly corrected these abnormalities. Furthermore, hyperglycemia-induced activation of RhoA/ROCK was reversed by treatment with rutin or the knockdown of ROCK2. Interestingly, rutin prevented hyperglycemia-induced hyperpermeability, and dysfunction of the tight junction, a high level of reactive oxygen species, and activation of RhoA/ROCK were significantly abolished with the knockdown of Nrf2. In conclusion, rutin significantly prevented hyperglycemia-disrupted renal endothelial barrier function by inhibiting the RhoA/ROCK signaling pathway through decreasing reactive oxygen species, which was mediated by the activation of Nrf2. Our results may explain, at least in part, some beneficial effects of rutin that may be applicable to the treatment of vascular disorders in diabetic nephropathy.

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“…The pathogenesis of diabetic nephropathy involve various mechanism and include hyperglycaemic condition, polyol pathway activation, renin-angiotensin system, reactive oxygen species (ROS), activation of protein kinase C (PKC) pathway, increase of advanced glycation end-product (AGE) and glomerular hyperfiltration [1,2]. Interaction of extracellular AGE with Receptor for Advanced Glycation End Products (RAGE) increases angiotensin II on Renin Angiotensin-Aldosterone System (RAAS) and activation of protein kinase c (PKC) which induce alterations in nephrin mRNA expression [3,4].…”

mentioning

confidence: 99%

Role of Antibody Anti-AGE in the Expression of Nephrin and RAGE on Primary Glomerulus Cell Exposed with AGE

Salam

Lyrawati

Samsu

2017

JTLS

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Nephrin is associated with the initial stage of the loss of the permeability barrier in diabetic nephropathy. Interaction AGE-RAGE increases angiotensin II on Renin Angiotensin-Aldosterone System (RAAS) and activation of protein kinase c (PKC) which induce alterations in nephrin mRNA expression. Alterations of nephrin expression induce transformation of slit membrane structure and the permeability changes at the glomerular filtration barrier. Anti-AGE vaccination once may cause the changes of nephrin and RAGE expression and can prevent progression of diabetic nephropathy. This study used primary glomerulus cell culture obtained from renal of Wistar rat aged 3 months, weighing 200-300 grams and assigned into negative control group that exposed to BSA 100 µg/mL, positive control group that exposed to AGE-BSA 100 µg/mL, treatment group 1 that exposed to polyclonal anti-AGE antibody 5 µg/mL and AGE-BSA 100 µg/mL and treatment group 2 that exposed to monoclonal anti-CML antibody 5 µg/mL and AGE-BSA 100 µg/mL. Paired t-test with a 0.05 level of confidence results showed that there were significantly different v in level of RAGE expression between experimental groups with control groups. Administration of polyclonal anti-AGE antibody decreased RAGE expression compared to negative control (p = 0.188) and positive control (p = 0.000). RAGE expression did not differ significantly in administration of monoclonal anti-CML antibody compared to negative control but significant with positive control. Administration of monoclonal anti-CML antibody inhibited increasing of nephrin expression compared to negative and positive control (p = 0.73; 0.125). In conclusion, this study suggested that administration of polyclonal anti-AGE or monoclonal anti-CML antibody could inhibit increasing of RAGE and nephrin expression in glomerulus primary culture that exposed to AGE which is expected to prevent the progression of diabetic nephropathy.

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Cell biology of diabetic nephropathy: Roles of endothelial cells, tubulointerstitial cells and podocytes

Cited by 165 publications

References 149 publications

Podocyte‐derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

Podocyte‐derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

Rutin Prevents High Glucose-Induced Renal Glomerular Endothelial Hyperpermeability by Inhibiting the ROS/Rhoa/ROCK Signaling Pathway

Role of Antibody Anti-AGE in the Expression of Nephrin and RAGE on Primary Glomerulus Cell Exposed with AGE

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