scholarly journals LY333531, a PKCβ inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1

2017 ◽  
Vol 38 (7) ◽  
pp. 1009-1023 ◽  
Author(s):  
Zhi-bin Wang ◽  
Su Zhang ◽  
Ya Li ◽  
Rong-mei Wang ◽  
Ling-chang Tong ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Early Stage ◽  
Endothelial Cell Apoptosis ◽  
Glomerular Endothelial Cell

XCL1 Aggravates Diabetic Nephropathy-Mediated Renal Glomerular Endothelial Cell Apoptosis and Inflammatory Response via Regulating p53/Nuclear Factor-Kappa B Pathway

Nephron ◽  
2021 ◽  
pp. 1-15
Author(s):  
Yuan Zhang ◽  
Xiaolan Chen ◽  
Yaping Fan ◽  
Jing Liu ◽  
Li Yuan
Keyword(s):  
Diabetic Nephropathy ◽  
Endothelial Cell ◽  
Inflammatory Response ◽  
Regression Model ◽  
Cell Apoptosis ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Lasso Regression ◽  
Endothelial Cell Apoptosis ◽  
Glomerular Endothelial Cell

<b><i>Background:</i></b> Glomerular endothelial cell damage plays an important role in the occurrence and development of diabetic nephropathy (DN). <b><i>Objectives:</i></b> This study aimed to clarify the role of XCL1 in DN-mediated glomerular endothelial cell apoptosis and whether the function was related to the activation of the p53/nuclear factor-kappa B (NF-κB) signaling pathway. <b><i>Methods:</i></b> Candidate biomarkers were identified by least absolute shrinkage and selection operator (LASSO) regression model analysis. The area under the receiver operating characteristic curve value was calculated and used to evaluate the discriminating ability. Cell viability, apoptosis, and interleukin-1β and tumor necrosis factor-α expression at messenger RNA and protein levels were detected by using the Cell Counting Kit-8, flow cytometry, ELISA, real-time polymerase chain reaction, and Western blotting assays. In vivo studies were conducted in the DN mice. <b><i>Results:</i></b> The LASSO regression model displayed good discriminating performance, with a C-index of 0.803 and good calibration, and high XCL1 expression was identified as the predicting factor for DN in diabetes mellitus patients. XCL1 expression was upregulated in glomeruli of db/db mice, which was closely related to the expression of its receptor (XCR1). XCL1 overexpression played an important role in the apoptosis and inflammatory response of high glucose (HG)-treated human renal glomerular endothelial cells. Meanwhile, the expression of p53 and the levels of inflammatory cytokines were upregulated upon XCL1 overexpression. p53 silencing with its inhibitor blocked the apoptotic response and inflammatory response in XCL1-overexpressed cells exposed to HG. Besides, the XCL1 overexpression-induced downregulation of NF-κB was reversed by pifithrin-α pretreatment. <b><i>Conclusions:</i></b> Our findings in this work provided the mechanistic insights into the effects of XCL1 on the modulation of DN development, illustrating that XCL1 might serve as an essential prognostic indicator and therapeutic target for DN progression.

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 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.

scholarly journals Uric acid promotes oxidative stress and enhances vascular endothelial cell apoptosis in rats with middle cerebral artery occlusion

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Chengfu Song ◽  
Xiangdong Zhao
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Vascular Endothelial Cell ◽  
Artery Occlusion ◽  
Vascular Endothelial ◽  
Endothelial Cell Apoptosis ◽  
Related Factors ◽  
Cerebral Artery Occlusion

In patients with cerebral infarction (CI), elevated serum uric acid (UA) level may exacerbate the occurrence and development of carotid atherosclerosis (AS). Our study intended to explore the underlying mechanism. We enrolled 86 patients with CI, and divided them into four groups: Non-AS, AS-mild, AS-moderate, and AS-severe groups; the levels of UA and oxidative stress-related factors in serum were detected. The middle cerebral artery occlusion (MCAO) model was used to stimulate CI in rats, and different doses of UA were administrated. The levels of oxidative stress-related factors in serum were detected. Hematoxylin & eosin (H&E) staining was used to observe the morphological alterations, and the apoptotic cell death detection kit was used to detect apoptotic cells. Increased UA concentration and enhanced oxidative stress were found in AS patients. H&E staining results showed that UA treatment exacerbated morphological damage in rats with MCAO, promoted oxidative stress, and enhanced vascular endothelial cell apoptosis in rats with MCAO.

Maternal Anti-HPA-1a Antibodies Increase Endothelial Cell Apoptosis and Permeability

2021 ◽  
pp. 1-9
Author(s):  
Rima Dardik ◽  
Ophira Salomon
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Intracranial Hemorrhage ◽  
Cell Apoptosis ◽  
Endothelial Damage ◽  
Αvβ3 Integrin ◽  
Endothelial Cell Apoptosis ◽  
Vascular Beds ◽  
Alloimmune Thrombocytopenia

Intracranial hemorrhage (ICH) associated with fetal/neonatal alloimmune thrombocytopenia (FNAIT) is attributed mainly to endothelial damage caused by binding of maternal anti-HPA-1a antibodies to the αvβ3 integrin on endothelial cells (ECs). We examined the effect of anti-HPA-1a antibodies on EC function using 2 EC lines from different vascular beds, HMVEC of dermal origin and hCMEC/D3 of cerebral origin. Anti-HPA-1a sera significantly increased apoptosis in both HMVEC and hCMEC/D3 cells and permeability in hCMEC/D3 cells only. This increase in both apoptosis and permeability was significantly inhibited by a monoclonal anti-β3 antibody (SZ21) binding to the HPA-1a epitope. Our results indicate that (1) maternal anti-HPA-1a antibodies impair EC function by increasing apoptosis and permeability and (2) ECs from different vascular beds vary in their susceptibility to pathological effects elicited by maternal anti-HPA-1a antibodies on EC permeability. Examination of maternal anti-HPA-1a antibodies for their effect on EC permeability may predict potential ICH associated with FNAIT.

scholarly journals Targeted Induction of Lung Endothelial Cell Apoptosis Causes Emphysema-like Changes in the Mouse

2008 ◽  
Vol 283 (43) ◽  
pp. 29447-29460 ◽  
Author(s):  
Ricardo J. Giordano ◽  
Johanna Lahdenranta ◽  
Lijie Zhen ◽  
Ugonma Chukwueke ◽  
Irina Petrache ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Endothelial Cell Apoptosis
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