scholarly journals Propyl Gallate Plays a Nephroprotective Role in Early Stage of Diabetic Nephropathy Associated with Suppression of Glomerular Endothelial Cell Proliferation and Angiogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Shaojiang Tian ◽  
Junming Tang ◽  
Huihui Liu ◽  
Liping Wang ◽  
Jianming Shen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Diabetic Nephropathy ◽  
Endothelial Cell ◽  
Propyl Gallate ◽  
Early Stage ◽  
Diabetic Rats ◽  
Endothelial Cell Proliferation ◽  
Glomerular Endothelial Cell ◽  
Enos Expression ◽  
Matrix Expansion

There is growing evidence suggesting that glomerular endothelial cell proliferation and angiogenesis may be responsible for the pathophysiological events in the early stage of diabetic nephropathy. This study was designed to investigate the factors related to glomerular endothelial cell proliferation and glomerular angiogenesis and assess the effect of propyl gallate on preventing these disorders in diabetic rats. We found that glomerular hypertrophy, glomerular mesangial matrix expansion, and albuminuria were significantly increased in DN rats. CD31+ endothelial cells significantly increased in glomerulus of diabetic rats. Double immunofluorescence staining showed some structurally defective vasculus tubes in glomerulus. Real-time PCR and western blot demonstrated the glomerular eNOS expression remained at the same level, while remarkable decreased NO productions and suppressed eNOS activities were observed in diabetic rats. Treatment with propyl gallate improved glomerular pathological changes, reduced endothelial cell proliferation, decreased albuminuria, and restored eNOS activity, but did not alter eNOS expression. These data suggest that endothelial cell proliferation and immature angiogenesis may be the contributors to progression of DN. Propyl gallate is a potential novel therapeutic agent on prevention of diabetic nephropathy.

scholarly journals Everolimus inhibits glomerular endothelial cell proliferation and VEGF, but not long-term recovery in experimental thrombotic microangiopathy

2006 ◽  
Vol 21 (10) ◽  
pp. 2724-2735 ◽  
Author(s):  
Katja Keller ◽  
Christoph Daniel ◽  
Harald Schöcklmann ◽  
Karl-Hans Endlich ◽  
Dontscho Kerjaschki ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Thrombotic Microangiopathy ◽  
Endothelial Cell Proliferation ◽  
Glomerular Endothelial Cell

scholarly journals Thrombospondin peptides are potent inhibitors of mesangial and glomerular endothelial cell proliferation in vitro and in vivo

1999 ◽  
Vol 55 (6) ◽  
pp. 2236-2249 ◽  
Author(s):  
Christian P.M. Hugo ◽  
Raimund P. Pichler ◽  
Eckhard Schulze-Lohoff ◽  
Felicitas Pröls ◽  
Stephen Adler ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Endothelial Cell Proliferation ◽  
Glomerular Endothelial Cell ◽  
Proliferation In Vitro

Regulation of bovine glomerular endothelial cell growth in vitro

1989 ◽  
Vol 256 (1) ◽  
pp. C182-C189 ◽  
Author(s):  
B. J. Ballermann
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Endothelial Cell Proliferation ◽  
Fibroblast Growth ◽  
Glomerular Endothelial Cell ◽  
Glomerular Endothelial Cells ◽  
Endothelial Cell Growth

To enable the study of glomerular endothelial cell functions and interactions with other glomerular cells, bovine glomerular capillary endothelial cells were established in culture. Selective media were used to facilitate endothelial cell proliferation and to suppress glomerular mesangial cell growth. Glomerular endothelial cells were separated from other cell types by fluorescence-activated cell sorting or, alternatively, by cloning. Glomerular endothelial cells expressed angiotensin I-converting enzyme and factor VIII activity and acetylated LDL uptake, properties generally held to be specific for endothelial cells. Proliferation of subconfluent glomerular endothelial cells was stimulated by basic fibroblast growth factor and, in the presence of heparin sodium, by acidic fibroblast growth factor. Platelet-derived growth factor was without effect on glomerular endothelial cell proliferation. Coculture with mesangial cells markedly inhibited proliferation of subconfluent glomerular endothelial cells. By contrast, medium conditioned by confluent glomerular endothelial cells markedly enhanced proliferation of subconfluent glomerular endothelial cells. These findings suggest that glomerular endothelial cell growth is under autocrine and paracrine control.

Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease

2007 ◽  
Vol 292 (6) ◽  
pp. F1665-F1672 ◽  
Author(s):  
Takahiko Nakagawa
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Diabetic Nephropathy ◽  
Endothelial Cell ◽  
Kidney Disease ◽  
Endothelial Cell Proliferation ◽  
No Bioavailability ◽  
Endothelial Nitric Oxide ◽  
Stimulation Of

In many forms of experimental kidney diseases, renal VEGF is low, and administering VEGF can be shown to be protective. A paradox occurs in diabetes, in which renal VEGF levels are high and a deleterious effect of VEGF on kidney disease has been shown. We have hypothesized that endothelial dysfunction induced by hyperglycemia or other factors may underlie the pathogenic mechanisms of a high VEGF state. VEGF normally stimulates endothelial nitric oxide (NO) release and acts in concert with elevated NO levels as a trophic factor for vascular endothelium. The increased NO derived from the endothelial cell acts as an inhibitory factor that prevents excess endothelial cell proliferation, vascular smooth muscle cell proliferation, and macrophage infiltration. In the setting where NO bioavailability is reduced in diabetes, high levels of VEGF lead to excessive endothelial cell proliferation, stimulation of macrophage chemotaxis, and vascular smooth muscle cell activation. Consistent with this hypothesis is our recent observation that diabetes induced in endothelial NO-deficient mice results in clinical and histological features identical to human diabetic nephropathy. The discovery of the key role for impaired endothelial NO bioavailability in the stimulation of VEGF and VEGF-dependent disease may provide key insights into not only the pathogenesis of diabetic nephropathy but also the utility and hazard of administering VEGF as a treatment for kidney disease.

scholarly journals Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling

2017 ◽  
Vol 44 (6) ◽  
pp. 2378-2394 ◽  
Author(s):  
Biyu Hou ◽  
Guifen Qiang ◽  
Yuerong Zhao ◽  
Xiuying Yang ◽  
Xi Chen ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Endothelial Cell ◽  
Early Stage ◽  
Cell Permeability ◽  
Glomerular Endothelial Cell ◽  
Salvianolic Acid ◽  
Structural Deterioration ◽  
Salvianolic Acid A

Background/Aims: Glomerular endothelium dysfunction leads to the progression of renal architectonic and functional abnormalities in early-stage diabetic nephropathy (DN). Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. This study investigated the role of Salvianolic acid A (SalA) on early-stage DN and its possible underlying mechanism. Methods: In vitro AGEs formation and breaking rate were measured to illustrate the effect of SalA on AGEs. Type 2 diabetic nephropathy rats were induced by high-fat diet and low-dose streptozocin (STZ). After eight-week treatment with SalA 1 mg/kg/day, 24h-urine protein, creatinine clearance was tested and renal structural injury was assessed by PAS and PASM staining. Primary glomerular endothelial cell permeability was evaluated after exposed to AGEs. AGEs-induced RhoA/ROCK and subsequently activated disarrange of cytoskeleton were assessed by western blot and immunofluorescence. Results: Biochemical assay and histological examination demonstrated that SalA markedly reduced endothelium loss and glomerular hyperfiltration, suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced urinary albumin and ameliorated renal function. Further investigation suggested that SalA exerted its renoprotective effects through inhibiting AGE-RAGE signaling. It not only inhibited formation of AGEs and increased its breaking in vitro, but also reduced AGEs accumulation in vivo and downregulated RAGE expression. SalA restored glomerular endothelial permeability through suppressing AGEs-induced rearrangement of actin cytoskeleton via AGE-RAGE-RhoA/ ROCK pathway. Moreover, SalA attenuated oxidative stress induced by AGEs, subsequently alleviated inflammation and restored the disturbed autophagy in glomerular endothelial cell and diabetic rats via AGE-RAGE-Nox4 axis. Conclusion: Our study indicated that SalA restored glomerular endothelial function and alleviated renal structural deterioration through inhibiting AGE-RAGE, thus effectively ameliorated early-stage diabetic nephropathy. SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.

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