Acute and Long-Term Changes Observed in Imprints of Mouse Mesothelium Exposed to Glucose-Enriched, Lactated, Buffered Dialysis Solutions

Gotloib, Lázaro; Waisbrut, Valery; Shostak, Avshalom; Kushnier, Raisa

doi:10.1159/000188647

Cited by 63 publications

(65 citation statements)

References 15 publications

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“…29,30 Oxidative stress and inflammation are associated with premature deaths from CVD in patients with ESRD. 31 Oxidative stress level may be regulated by apelin expression and secretion to prevent excessive lipid accumulation and formation of reactive oxygen products in differentiated adipocytes. 32 El-Shehaby et al investigated whether circulating apelin levels reflect cardiovascular homeostasis and inflammation in HD patients.…”

Section: Discussionmentioning

confidence: 99%

The relation between apelin levels, echocardiographic findings and carotid intima media thickness in peritoneal dialysis patients

et al. 2015

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Background: Cardiovascular disease (CVD) is the most important cause of morbidity and mortality in patients with end stage renal disease (ESRD). Apelin expressed in endothelial and other tissues including brain and kidney is an adipocytokine defined recently and is emerging an important mediator of cardiovascular homeostasis. The aim of this study was to test whether apelin levels might be associated with carotid artery atherosclerosis and left ventricular mass index (LVMI) in peritoneal dialysis patients. Patients and methods: Fifty peritoneal dialysis patients (25 female, mean age 41.4 ± 11.9 years, mean dialysis vintage 65.0 ± 35.4 months) and 18 healthy individuals (9 female, mean age 41.7 ± 6.8 years) were included in this cross-sectional study. Serum apelin 12 levels, echocardiographic findings and carotid intima media thickness (CIMT) were recorded as well as clinical and laboratory data. Results: There were no differences between the patient and the control groups with regard to demographic characteristics. In patient group, LVMI, CIMT, CRP and apelin levels were elevated compared to control group. However there was no association between apelin, LVMI and CIMT. There was a positive correlation between apelin and CRP, which was not statistically significant. When patients were divided into two groups according to the mean serum apelin levels, LVMI, CIMT and CRP were higher in the high apelin group but this difference did not reach statistical significance. Conclusion: We observed an increased inflammation and CVD risk in peritoneal dialysis patients. However, serum apelin levels seem not to be associated with cardiovascular risk in this group of patients.

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Section: Discussionmentioning

confidence: 99%

The relation between apelin levels, echocardiographic findings and carotid intima media thickness in peritoneal dialysis patients

et al. 2015

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“…Adv-LacZ encodes the enzyme ␤-galactosidase, which can be detected enzymatically using X-gal as a substrate. For X-gal staining, the abdominal wall tissues were incubated with 1 mg/ml X-gal (Amresco, Inc., Solon, OH) for 4 h at 37°C in PBS solution containing 35 mM K 3 Fe(CN) 6 , 35 mM K 4 Fe(CN) 6 , 2 mM MgCl 2 , 0.02% NP-40, and 0.01% sodium deoxycholate. The tissues were embedded in graded (10 to 30%) sucrose solution and then OCT solution for frozen section.…”

Section: Animal Model Of Pdmentioning

confidence: 99%

“…4 High glucose (HG) itself is proved to induce a profibrotic and proinflammatory reaction. 5,6 HG upregulates the expression of ␤1 (TGF-␤1), 7,8 vascular endothelial growth factor, 9 and monocyte chemoattractant peptide-1 10 with an induction of apoptosis of peritoneal mesothelial cells. 11 Most HG-associated effects were known to be mediated primarily by glucose itself or GDP, depending on parameters used for assessing functional and structural changes in peritoneal membrane or cells.…”

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confidence: 99%

HGF and BMP-7 Ameliorate High Glucose–Induced Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelium

Shin

Kim

et al. 2009

Journal of the American Society of Nephrology

117

130

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Over time, peritoneal dialysis results in functional and structural alterations of the peritoneal membrane, but the underlying mechanisms and whether these changes are reversible are not completely understood. Here, we studied the effects of high levels of glucose, which are found in the dialysate, on human peritoneal mesothelial cells (HPMCs). We found that high concentrations of glucose induced epithelialto-mesenchymal transition (EMT) of HPMC, suggested by decreased expression of E-cadherin and increased expression of ␣-smooth muscle actin, fibronectin, and type I collagen and by increased cell migration. Normalization of glucose concentration on day 2 reversed the phenotypic transformation, but the changes were irreversible after 7 d of stimulation with high glucose. In addition, exposure of HPMC to high glucose resulted in a decreased expression of the antifibrotic cytokines, hepatocyte growth factor (HGF) and bone morphogenic protein 7 (BMP-7). Exogenous treatment with HGF resulted in a dosage-dependent prevention of high glucose-induced EMT. Both BMP-7 peptide and gene transfection with an adenoviral vector of BMP-7 also protected HPMCs from EMT. Furthermore, adenoviral BMP-7 transfection decreased peritoneal EMT and ameliorated peritoneal thickening in an animal model of peritoneal dialysis. In summary, high concentrations of glucose induce a reversible EMT of HPMCs, associated with decreased production of HGF and BMP-7. Treatment of HPMCs with HGF or BMP-7 blocks high glucose-induced EMT, and BMP-7 ameliorates peritoneal fibrosis in an animal model of peritoneal dialysis.

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“…Therefore, the detrimental impact of high glucose (HG) on mesothelial cells may contribute to the peritoneal membrane dysfunction during dialysis. In a series of experiments, Gotloib et al 4,5 analyzed the imprints of the mesothelium obtained from mice exposed chronically to glucose-containing PDF. They found a significant increase in both the average size of mesothelial cell and the prevalence of very large cells, which together resulted in reduced density of the mesothelial monolayer.…”

mentioning

confidence: 99%

Accelerated senescence of human peritoneal mesothelial cells exposed to high glucose: the role of TGF-β1

Książek

Korybalska

Jörres

et al. 2007

Laboratory Investigation

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Cellular senescence can be activated in response to noxious environmental stimuli. A senescent-like phenotype has been detected in the peritoneal mesothelium of mice exposed to high intraperitoneal glucose. We have sought to examine whether high glucose (HG) can induce the senescence program in human peritoneal mesothelial cells (HPMC) in vitro. Senescence of omentum-derived HPMC was induced by serial passages. Cells were cultured in media containing either 5 mM glucose, 30 mM glucose, or 5 mM glucose and 25 mM mannitol (M) for osmotic control. Compared with HPMC cultured in low glucose, the growth rate of cells exposed to HG was significantly decreased so that the cells reached fewer population doublings before entering senescence. Exposure to HG led to increased expression of senescence-associated b-galactosidase (SA-b-Gal) and of the cell cycle inhibitors p21 Waf1 and p27 Kip1 . Late-passage HPMC exposed to HG displayed marked hypertrophy and released increased amounts of fibronectin and TGF-b1. These effects were absent from HPMC treated with equimolar M. Exposure of early-passage HPMC to exogenous recombinant TGF-b1 induced a senescence marker SA-b-Gal in a dose-dependent manner and mimicked other senescence-associated alterations induced by HG. The addition of anti-TGF-b1 neutralizing antibody partially reduced the activation of HG-induced SA-b-Gal. These results indicate that chronic exposure to elevated glucose may result in TGF-b1-mediated accelerated senescence of HPMC in vitro, which may hypothetically contribute to the peritoneal membrane dysfunction during peritoneal dialysis in vivo.

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Acute and Long-Term Changes Observed in Imprints of Mouse Mesothelium Exposed to Glucose-Enriched, Lactated, Buffered Dialysis Solutions

Cited by 63 publications

References 15 publications

The relation between apelin levels, echocardiographic findings and carotid intima media thickness in peritoneal dialysis patients

The relation between apelin levels, echocardiographic findings and carotid intima media thickness in peritoneal dialysis patients

HGF and BMP-7 Ameliorate High Glucose–Induced Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelium

Accelerated senescence of human peritoneal mesothelial cells exposed to high glucose: the role of TGF-β1

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