Advanced glycation end-products induce cell cycle arrest and hypertrophy in podocytes

Rüster, Christiane; Bondeva, Tzvetanka; Franke, Sybille; Förster, Martin; Wolf, Günter

doi:10.1093/ndt/gfn085

Cited by 54 publications

(75 citation statements)

References 49 publications

(74 reference statements)

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“…8) Control nonglycated BSA was incubated without glucose using the above same procedure. At the end of the incubation period, samples were dialyzed extensively against PBS at 4°C to remove unreacted glucose.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Reactive Oxygen Species/Extracellular Signal-Regulated Kinases Pathway by Pioglitazone Attenuates Advanced Glycation End Products-Induced Proliferation of Vascular Smooth Muscle Cells in Rats

Yuan

Zhang²,

Gong³

et al. 2011

Biological & Pharmaceutical Bulletin

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Advanced glycation end products (AGEs) have been shown to induce the proliferation of vascular smooth muscle cells (VSMCs) and contribute to atherogenesis and diabetes. In the present study, we investigated the effects of pioglitazone, a peroxisome proliferator activated receptor gamma (PPARg g) agonist, on AGE-induced rat VSMC growth and the underlying mechanism. In cultured rat VSMCs, AGE treatment induced VSMC proliferation in time-and dose-dependent manner, while down-regulated the expression of PPARg g. Pretreatment of pioglitazone not only prevented the down-regulation of PPARg g, but inhibited VSMC proliferation and prevented S-phase entry of cell via a G0-G1 block in the presence of AGEs. Western blotting analysis showed that AGE treatment potentiated to activate extracelluar signal-regulated kinases (ERK1/2) by the induction of intracellular reactive oxygen species (ROS) production, since ROS scavenger N-acetyl-L-cysteine pretreatment significantly inhibited AGE-induced ERK1/2 activation. Further, pretreatment with either N-acetyl-L-cysteine or the inhibitor of ERK1/2 activation suppressed AGE-induced proliferation of VSMCs, suggesting a role of ROS/ERK1/2 signaling. Notably, we demonstrated that pretreatment of pioglitazone significantly attenuated AGE-induced ROS and ERK1/2 activation. Collectively, these results suggest that pioglitazone inhibits AGE-induced VSMC proliferation via increasing PPARg g expression and inhibiting ROS/ERK1/2 signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Inhibition of Reactive Oxygen Species/Extracellular Signal-Regulated Kinases Pathway by Pioglitazone Attenuates Advanced Glycation End Products-Induced Proliferation of Vascular Smooth Muscle Cells in Rats

Yuan

Zhang²,

Gong³

et al. 2011

Biological & Pharmaceutical Bulletin

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show abstract

“…Then, subcultivation under non-permissive conditions without INF-γ was started at 37°C with media changed on alternate days. Differentiation of podocytes grown for 10 days at 37°C was confirmed by the podocyte marker synaptopodin (polyclonal rabbit antibody SE-19; Sigma, St. Louis, Mo., USA) and validated by immunocytological staining and Western blot as previously described [13]. All experiments were conducted in RPMI medium containing 0.1% FCS.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were then stimulated with ANG II (10 –7 mol/l; Sigma-Aldrich, USA) [14] in the presence or absence of losartan (10 –6 mol/l losartan; gift of Merck Sharp & Dohme Research Laboratories, Munich, Germany) or PD123319 (10 –6 mol/l; Sigma-Aldrich, USA). In further experiments, cells were additionally stimulated with AGE-BSA (5 mg/ml) [13]. …”

Section: Methodsmentioning

confidence: 99%

“…CML was measured by an ELISA (Roche Diagnostics GmbH, Mannheim, Germany), whereas pentosidine was determined by HPLC (Merck-Hitachi, Darmstadt, Germany) as previously described [15]. AGE uptake by podocytes was confirmed by Western blot analysis for the detection of CML-modified albumin (polyclonal rabbit antibody; Roche Diagnostics) as recently reported [13]. …”

Section: Methodsmentioning

confidence: 99%

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Angiotensin II Upregulates RAGE Expression on Podocytes: Role of AT2 Receptors

et al. 2009

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Background: Advanced glycation end products (AGEs) play an important role in diabetic nephropathy. The receptor for AGEs, called RAGE, is present on podocytes. We investigated whether angiotensin II (ANG II) modulates RAGE expression on cultured differentiated podocytes. Results: Cultured podocytes expressed AT1 and AT2 receptors. Surprisingly, ANG II induced RAGE mRNA and protein expression through AT2 receptors. ANG II had no influence on proliferation or protein content of podocytes. The increase in RAGE expression depended on stimulated transcriptional activity. Using various mutant reporter constructs of the RAGE promoter region, it was shown that a NF-κB binding site at –1519 was essential for ANG II-induced transcriptional activity. Preincubation with ANG II increased the expression of tumor necrosis factor-α mRNA and protein expression induced by AGE, indicating that the ANG II-mediated upregulation of RAGE has functional consequences. AGE-BSA was incorporated into cells as measured by Western blots for Nε-carboxymethyllysine, but ANG II did not influence this process. ANG II in the absence or presence of AGE-BSA did not induce apoptosis of podocytes. Conclusion: Our study revealed aninteraction between the renin-angiotensin system and the AGE/RAGE axis in podocytes. Since intraglomerular ANG II levels are increased in diabetic nephropathy, this interaction may have pathophysiological consequences for podocyte injury and inflammation associated with the development of diabetic nephropathy.

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“…22,23 Advanced glycation end-products have been implicated in diabetic complications, and in nephropathy patients, their concentrations are high resulting in induction of proteinuria. 24 Impairment of wound healing is a major factor in Diabetic Foot, and advanced glycation endproducts have also been implicated in this process. The blocking of advanced glycation end-products improves diabetic nephropathy as well as restoring effective wound healing in diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Diabetic Foot Amputation; Frequency of Diabetic Nephropathy Among Patients

Akhtar¹,

Ahmed²,

Tabassum³

et al. 2017

TPMJ

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ABSTRACT… Introduction: Diabetic foot lesions have remained a major cause of morbidity in patients with kidney failure. Foot complications are more than twofolds in diabetic nephropathy patients, and the rate of amputation is 6 to 10 times higher in diabetic nephropathy patients in comparison to the general diabetic population. Objectives: To determine the frequency of diabetic nephropathy in patients undergoing diabetic foot amputation. Study Design: Observational cross-sectional study. Setting: Surgical Department Unit-II, Sheikh Zayed Medical College and Hospital Rahim Yar khan. Material and Methods: The duration of the study was 2 years from Dec-2013 to Dec-2015. A total number of 73 patients were included in this study. Patients who were admitted to the department of surgery for amputation of the foot or the leg having the history of diabetes regardless of their age and sex were selected for this study. Data analyses were carried out using SPSS Version17 software. Quantitative variables were presented as Mean and standard deviations. Frequency and percentages were computed for qualitative variables. Results: The mean age of the patients was 57.51±7.61 years. Out of 73 cases, there were 43(58.9%) males and 30 (41.1%) females. Previous history of amputation was observed in 26 (35.62%) cases, 48 (65.75%) patients were hypertensive. Out of 73 patients, Forty (54.79%) had controlled diabetes and 33 (45.21%) had uncontrolled diabetes. Twenty seven patients (36.99%) were diagnosed for diabetic nephropathy. The incidence of nephropathy was high in patients with advancing age. This incidence was in 26 (56.62%) patients with age 51 to 60 years and 18 (39.13%) in patients having age more than 60 years. Conclusions: Lower extremity amputations are strongly associated with nephropathy in diabetic patients. It is very important to check and improve the renal function in patients with diabetic foot ulcers who are hypertensive, increasing age and long duration of DM to prevent lower limb amputations. Key words:Diabetes mellitus (DM), Nephropathy, Diabetic foot amputation.

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Advanced glycation end-products induce cell cycle arrest and hypertrophy in podocytes

Abstract: Background. Podocyte injury with loss of cells into the urine seems to be an early factor in diabetic nephropathy.

Cited by 54 publications

References 49 publications

Inhibition of Reactive Oxygen Species/Extracellular Signal-Regulated Kinases Pathway by Pioglitazone Attenuates Advanced Glycation End Products-Induced Proliferation of Vascular Smooth Muscle Cells in Rats

Inhibition of Reactive Oxygen Species/Extracellular Signal-Regulated Kinases Pathway by Pioglitazone Attenuates Advanced Glycation End Products-Induced Proliferation of Vascular Smooth Muscle Cells in Rats

Angiotensin II Upregulates RAGE Expression on Podocytes: Role of AT2 Receptors

Diabetic Foot Amputation; Frequency of Diabetic Nephropathy Among Patients

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