Anti-inflammatory effects of pigment epithelium-derived factor in diabetic nephropathy

2008 ◽  
Vol 294 (5) ◽  
pp. F1166-F1173 ◽  
Author(s):  
Joshua J. Wang ◽  
Sarah X. Zhang ◽  
Robert Mott ◽  
Ying Chen ◽  
Ryan R. Knapp ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
High Glucose ◽  
Matrix Protein ◽  
Pigment Epithelium ◽  
Diabetic Rats ◽  
Renoprotective Effect ◽  
Pigment Epithelium Derived Factor ◽  
Control Virus ◽  
Anti Inflammatory ◽  
Proinflammatory Factors

Previously, we have reported that pigment epithelium-derived factor (PEDF) ameliorates albuminuria and inhibits matrix protein deposition in the kidney of streptozotocin (STZ)-induced diabetic rats, suggesting a renoprotective effect of PEDF in early stages of diabetic nephropathy. As inflammation is a major contributor to the development and progression of diabetic nephropathy, we examined in the present study whether PEDF inhibits renal inflammation in diabetic kidney. Diabetic rats received an intravenous injection of an adenovirus expressing PEDF (Ad-PEDF) or the same titer of a control virus. Three wk after the injection, diabetic rats treated with the control virus showed significantly elevated renal levels of proinflammatory factors such as ICAM-1, MCP-1, TNF-α, and VEGF compared with age-matched nondiabetic controls. Ad-PEDF effectively suppressed the overexpression of these proinflammatory factors in diabetic kidneys. In cultured primary human renal mesangial cells (HMC), the high-glucose medium-induced upregulation of VEGF and MCP-1 was largely blocked by PEDF. Furthermore, PEDF inhibited high glucose-induced activation of NF-κB, a key transcription factor mediating inflammatory responses, and hypoxia-inducible factor-1, a major activator of VEGF expression in HMC. These results suggest that the renoprotective effect of PEDF against diabetic nephropathy may be partially through its anti-inflammatory activity, likely by blocking the NF-κB and HIF-1 pathways.

Decreased expression of pigment epithelium-derived factor within the penile tissues contributes to erectile dysfunction in diabetic rats

2018 ◽  
Vol 132 (20) ◽  
pp. 2175-2188 ◽  
Author(s):  
Hongjie Qiao ◽  
Yuanyuan Zhang ◽  
Wenwen Lin ◽  
Yu-Feng Wang ◽  
Cristina M. Furdui ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Erectile Dysfunction ◽  
Pigment Epithelium ◽  
Diabetic Rats ◽  
No Synthase ◽  
Inflammatory Factor ◽  
Potential Implication ◽  
Pigment Epithelium Derived Factor ◽  
Tnf Α ◽  
Anti Inflammatory

Increased production of reactive oxygen species (ROS) and inflammation are major contributors to the development and progression of diabetes-associated erectile dysfunction (DMED). As an endogenous antioxidant and anti-inflammatory factor, the potential implication of pigment epithelium-derived factor (PEDF) in DMED has not been revealed. To assess the potential antioxidant and anti-inflammatory functions of PEDF in DMED, we first demonstrated that PEDF was significantly decreased at the levels of the mRNA and protein in the penis of diabetic rats compared with normal controls. To test the hypothesis that decreased the penile levels of PEDF are associated with oxidative stress and inflammation in DMED, an adenovirus expressing PEDF (Ad-PEDF) or the same titer of control virus (Ad-GFP) was intracavernously administered at 2 weeks after diabetic onset. After 6 weeks of treatment, we found that administration of Ad-PEDF could significantly increase erectile response to cavernosal nerve stimulation in the diabetic rats by restoring the endothelial NO synthase (eNOS), P-eNOS, and neuronal NO synthase (nNOS) protein levels to the standard levels represented in normal rats and by suppressing the levels of tumor necrosis factor-α (TNF-α) and oxidative stress. In conclusion, the present data indicated that the antioxidant and anti-inflammatory potential of PEDF plays important role in restoring erectile function by the inhibition of oxidative stress and TNF-α production.

scholarly journals Protective Effects of Luteolin on Diabetic Nephropathy in STZ-Induced Diabetic Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Guo Guang Wang ◽  
Xiao Hua Lu ◽  
Wei Li ◽  
Xue Zhao ◽  
Cui Zhang
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Antioxidant Properties ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Sod Activity ◽  
Matrix Expression

Diabetic nephropathy is a long-term complication of diabetic mellitus. Many experimental evidences suggest that persistent hyperglycaemia generates intracellular reactive oxygen species (ROS) and upregulates transforming growth factor-b1 and extracellular matrix expression in mesangial and tubular epithelial cells, which is involved of free radicals in the pathogenesis of diabetes and more importantly in the development of diabetic complications. Antioxidants effectively inhibit high-glucose- and H2O2-induced transforming growth factor-b1 and fibronectin upregulation, thus providing evidence that ROS play an important role in high glucose-induced renal injury. The flavonoid luteolin has been shown to possess direct antioxidant activity, therefore we hypothesize that it may be useful in treatment of many chronic disease associated with oxidative stress, such as diabetic nephropathy via its antioxidant properties. Our results suggested that protection against development of diabetic nephropathy by luteolin treatment involved changes in superoxide dismutase (SOD) activity, the malondialdehyde (MDA) content and expression of Heme Oxygenase-1 (HO-1) protein.

Proteomic profile of primary isolated rat mesangial cells in high-glucose culture condition and decreased expression of PSMA6 in renal cortex of diabetic ratsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 635-648 ◽  
Author(s):  
Zhiguo Li ◽  
Haojun Zhang ◽  
Xi Dong ◽  
Frank J. Burczynski ◽  
Patrick Choy ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
High Glucose ◽  
Gel Electrophoresis ◽  
Renal Cortex ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Two Dimensional Gel Electrophoresis ◽  
Isolated Rat

Diabetic nephropathy (DN) is one of the most important complications of diabetic patients and is characterized histologically by an accumulation of extracellular matrix (ECM) protein in the glomerular mesangium. Therefore, mesangial cells likely play an important role in the development of diabetic nephropathy. Here, we employed proteomic techniques to investigate the protein profile of rat mesangial cells under high-glucose culture conditions. Primary isolated rat glomerular mesangial cells were cultured under different concentrations of glucose (5.4 mmol·L–1 for normal control and 30 mmol·L–1 for high glucose) for 0, 8, 16, and 72 h, as well as for 25 days. Cellular total proteins were isolated from these cells and employed for two-dimensional gel electrophoresis (2-DE). Differentially expressed proteins were identified by matrix-assisted laser desorption – ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and some of these proteins were documented in rat models of diabetes by Western blot. Rat mesangial cells were successfully isolated in the laboratory and their proliferation rates were significantly inhibited by high glucose. Two-dimensional gel electrophoresis analyses revealed 28 differentially expressed protein spots between the normal and high-glucose groups. After MALDI-TOF-MS analysis, all 28 protein spots were successfully identified with the peptide mass fingerprint (PMF) method. Representatively, SOD1, PCBP1 and PSMA6 were validated by Western blot analysis following protein extractions from the normal and high-glucose groups. Abundance of these proteins was consistent with that found in 2-DE. Moreover, expression of SOD1, PCBP1, and PSMA6 in renal cortex was further examined in two rat models of diabetes (streptozotocin-induced and spontaneous OLETF diabetic models). Abundance of SOD1 and PCBP1 proteins did not show any significant difference between normal control and diabetic rats. However, abundance of the PSMA6 protein was significantly reduced in the renal cortex of both STZ-induced and spontaneous OLETF diabetic rats. Proteomic analysis identified 28 differentially expressed proteins in primary isolated rat mesangial cells between normal and high glucose treatments. Expression of one identified protein was found to be consistent with expression in the renal cortex of two rat diabetic models. Therefore, identification of protein expression patterns in mesangial cells can be employed to develop a therapeutic target for treatment of diabetic nephropathy.

scholarly journals Decreased Expression of Pigment Epithelium-Derived Factor Is Involved in the Pathogenesis of Diabetic Nephropathy

Diabetes ◽  
2004 ◽  
Vol 54 (1) ◽  
pp. 243-250 ◽  
Author(s):  
J. J. Wang ◽  
S. X. Zhang ◽  
K. Lu ◽  
Y. Chen ◽  
R. Mott ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Pigment Epithelium ◽  
Pigment Epithelium Derived Factor

scholarly journals Knockdown of NLRP3 alleviates high glucose or TGFB1-induced EMT in human renal tubular cells

2018 ◽  
Vol 61 (3) ◽  
pp. 101-113 ◽  
Author(s):  
Shan Song ◽  
Duojun Qiu ◽  
Fengwei Luo ◽  
Jinying Wei ◽  
Ming Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
P38 Mapk ◽  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Inflammasome Activation ◽  
Mesenchymal Transition ◽  
Tubular Cells ◽  
Renal Tubular Cells

Tubular injury is one of the crucial determinants of progressive renal failure in diabetic nephropathy (DN), while epithelial-to-mesenchymal transition (EMT) of tubular cells contributes to the accumulation of matrix protein in the diabetic kidney. Activation of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome leads to the maturation of interleukin (IL)-1B and is involved in the pathogenic mechanisms of diabetes. In this study, we explored the role of NLRP3 inflammasome on high glucose (HG) or transforming growth factor-B1 (TGFB1)-induced EMT in HK-2 cells. We evaluated EMT through the expression of α-smooth muscle actin (α-SMA) and E-cadherin as well as the induction of a myofibroblastic phenotype. Reactive oxygen species (ROS) was observed using the confocal microscopy. HG was shown to induce EMT at 48 h, which was blocked byNLRP3silencing or antioxidant N-acetyl-L-cysteine (NAC). We found thatNLRP3interference could inhibit HG-induced ROS. Knockdown ofNLRP3could prevent HG-induced EMT by inhibiting the phosphorylation of SMAD3, P38 MAPK and ERK1/2. In addition, P38 MAPK and ERK1/2 might be involved in HG-induced NLRP3 inflammasome activation. Besides, TGFB1 induced the activation of NLRP3 inflammasome and the generation of ROS, which were blocked byNLRP3interference or NAC. Tubular cells exposed to TGFB1 also underwent EMT, and this could be inhibited byNLRP3shRNA or NAC. These results indicated that knockdown ofNLRP3antagonized HG-induced EMT by inhibiting ROS production, phosphorylation of SMAD3, P38MAPK and ERK1/2, highlighting NLRP3 as a potential therapy target for diabetic nephropathy.

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