PPARγ ligands attenuate mesangial contractile dysfunction in high glucose

Ueta, Maki; Wakisaka, Masanori; Ago, Tetsuro; Kitazono, Takanari; Nakamura, Udai; Yoshinari, Mototaka; Iwase, Masanori; Iida, Mitsuo

doi:10.1111/j.1523-1755.2004.00474.x

Cited by 13 publications

(9 citation statements)

References 58 publications

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“…This is in agreement with other studies which have demonstrated reduced urinary albumin excretion and renoprotection by thiazolidinediones [34–36]. The mechanisms for reduced protein excretion and renoprotection may be direct or indirect, due to the lowering of glucose levels or decreased blood pressure [35, 37–41]. …”

Section: Discussionsupporting

confidence: 92%

Effects of Chronic PPAR‐Agonist Treatment on Cardiac Structure and Function, Blood Pressure, and Kidney in Healthy Sprague‐Dawley Rats

Blasi

Heyen²,

Hemkens³

et al. 2009

PPAR Research

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PPAR-γ agonists have been associated with heart failure (HF) in diabetic patients. These incidences have been reported mostly in patient populations who were at high risk for HF or had pre-existing impaired cardiovascular function. However, whether there are similar effects of these agents in subjects with no or reduced cardiovascular pathophysiology is not clear. In this study, the effects of chronic treatment with PD168, a potent peroxisome proliferator activated receptor (PPAR) subtype-γ agonist with weak activity at PPAR-α, and rosiglitazone (RGZ), a less potent PPAR-γ agonist with no PPAR-α activity, were evaluated on the cardiovascular-renal system in healthy male Sprague-Dawley (SD) rats by serial echocardiography and radiotelemetry. Rats were treated with vehicle (VEH), PD168, @ 10 or 50 mg/kg·bw/day (PD-10 or PD-50, resp.) or RGZ @ 180 mg/kg·bw/day for 28 days (n = 10/group). Relative to VEH, RGZ, and both doses of PD168 resulted in a significant fall in blood pressure. Furthermore, RGZ and PD168 increased plasma volume (% increase from baseline) 18%, 22%, and 48% for RGZ, PD-10, and PD-50, respectively. PD168 and RGZ significantly increased urinary aldosterone excretion and heart-to-body weight ratio relative to VEH. In addition, PD168 significantly decreased (10–16%) cardiac ejection fraction (EF) and increased left ventricular area (LVA) in systole (s) and diastole (d) in PD-10 and -50 rats. RGZ significantly increased LVAd; however, it did not affect EF relative to VEH. In conclusion, chronic PPAR-γ therapy may predispose the cardiorenal system to a potential sequela of structural and/or functional changes that may be deleterious with regard to morbidity and mortality.

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Section: Discussionsupporting

confidence: 92%

Effects of Chronic PPAR‐Agonist Treatment on Cardiac Structure and Function, Blood Pressure, and Kidney in Healthy Sprague‐Dawley Rats

Blasi

Heyen²,

Hemkens³

et al. 2009

PPAR Research

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“…Conversely, decreased contraction of mesangial cells has been reported following exposure to long-term high glucose conditions [ 19 , 20 ]; this decrease is thought to be one of the underlying mechanisms for the hyperfiltration in diabetic nephropathy. We reported that the contractile response to angiotensin II decreases in cells after 5 days of exposure to 20 mM glucose [ 47 ]. In this study, the contractile response to angiotensin II in rat mesangial cells was abolished after 6 days incubation with 20 mM glucose.…”

Section: Discussionmentioning

confidence: 99%

Sodium Glucose Cotransporter 2 (SGLT2) Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells

Wakisaka

Nagao

Yoshinari³

2016

PLoS ONE

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PurposeMesangial cells play an important role in regulating glomerular filtration by altering their cellular tone. We report the presence of a sodium glucose cotransporter (SGLT) in rat mesangial cells. This study in rat mesangial cells aimed to evaluate the expression and role of SGLT2.MethodsThe SGLT2 expression in rat mesangial cells was assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Changes in the mesangial cell surface area at different glucose concentrations and the effects of extracellular Na+ and Ca2+ and of SGLT and Na+/Ca2+ exchanger (NCX) inhibitors on cellular size were determined. The cellular sizes and the contractile response were examined during a 6-day incubation with high glucose with or without phlorizin, an SGLT inhibitor.ResultsWestern blotting revealed an SGLT2 band, and RT-PCR analysis of SGLT2 revealed the predicted 422-bp band in both rat mesangial and renal proximal tubular epithelial cells. The cell surface area changed according to the extracellular glucose concentration. The glucose-induced contraction was abolished by the absence of either extracellular Na+ or Ca2+ and by SGLT and NCX inhibitors. Under the high glucose condition, the cell size decreased for 2 days and increased afterwards; these cells did not contract in response to angiotensin II, and the SGLT inhibitor restored the abolished contraction.ConclusionsThese data suggest that SGLT2 is expressed in rat mesangial cells, acts as a normal physiological glucose sensor and regulates cellular contractility in rat mesangial cells.

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“…Thiazolidinediones inhibit cell growth and reduce extracellular matrix production in human kidney fibroblasts through a reduction in the secretion of type IV collagen and fibronectin, a decrease in proline incorporation and a reduction of the activity of tissue inhibitor of metalloproteinase (TIMP)‐1, TIMP‐2, and metalloproteinase (MMP)‐9 39,40 . In addition, thiazolidinediones inhibit mesangial proliferation induced by vascular endothelial growth factor (VEGF) and platelet‐derived growth factor (PDGF), and attenuate mesangial contractile dysfunction 41–44 …”

Section: Anti‐inflammatory and Antiproliferative Effectsmentioning

confidence: 99%

Antiproteinuric and anti‐inflammatory effects of thiazolidinedione (Review Article)

Szeto

2008

Nephrology

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SUMMARY:Type 2 diabetes is the most common cause of chronic renal failure worldwide. Only a few oral antidiabetic drugs can be used for treating type 2 diabetes in patients with renal failure. Among them is thiazolidinedione, which is the agonist of peroxisome proliferator-activated receptor (PPAR)-g. PPAR-g receptors are expressed in many tissues including the kidney. Recently, beneficial effects of PPAR-g agonists on several aspects related to renal function have been reported. These drugs have been shown to have favourable haemodynamic and anti-inflammatory effects on the kidneys. On the other hand, there is a rising concern on the association between thiazolidinedione treatment and the risk of cardiovascular disease. In the present paper, we review the recent studies that evaluated these potential effects of thiazolidinedione in patients with kidney diseases.

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PPARγ ligands attenuate mesangial contractile dysfunction in high glucose

Cited by 13 publications

References 58 publications

Effects of Chronic PPAR‐Agonist Treatment on Cardiac Structure and Function, Blood Pressure, and Kidney in Healthy Sprague‐Dawley Rats

Effects of Chronic PPAR‐Agonist Treatment on Cardiac Structure and Function, Blood Pressure, and Kidney in Healthy Sprague‐Dawley Rats

Sodium Glucose Cotransporter 2 (SGLT2) Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells

Antiproteinuric and anti‐inflammatory effects of thiazolidinedione (Review Article)

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