scholarly journals Hirudin Reduces the Expression of Markers of the Extracellular Matrix in Renal Tubular Epithelial Cells in a Rat Model of Diabetic Kidney Disease Through the Hypoxia-Inducible Factor-1α (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway

2020 ◽  
Vol 26 ◽  
Author(s):  
Xinxin Pang ◽  
Yage Zhang ◽  
Xiujie Shi ◽  
Zining Peng ◽  
Yufeng Xing ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Kidney Disease ◽  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Vegf Signaling ◽  
Renal Tubular ◽  
Endothelial Growth Factor ◽  
Vegf Signaling Pathway

Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells

2000 ◽  
Vol 278 (6) ◽  
pp. F905-F915 ◽  
Author(s):  
John Kanellis ◽  
Scott Fraser ◽  
Marina Katerelos ◽  
David A. Power
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Survival Factor ◽  
Renal Tubular ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) acts primarily as an endothelial cell mitogen via the “endothelial cell-specific” receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR). Only a few nonendothelial cells have been shown to possess functional VEGF receptors. We therefore examined the rat renal tubular epithelial cell line NRK52-E. NRK52-E expressed VEGFR-1 and VEGFR-2 mRNA and protein by RT-PCR, Northern blotting, Western blotting, immunofluorescence, and ligand binding. Serum-starved NRK52-E incubated with VEGF showed a significant increase in [3H]thymidine incorporation compared with control (2.3-fold at 1–10 ng/ml, P < 0.05; 3.3-fold at 50–100 ng/ml, P < 0.01). VEGF also protected NRK52-E from hydrogen peroxide-induced apoptosis and necrosis compared with control (annexin-V-FITC-positive cells, 39 vs. 54%; viable cells, 50.5 vs. 39.7%). Immunohistochemical staining using a variety of antibodies showed expression of both VEGF receptors in normal rat renal tubules in vivo. Because VEGF induced a proliferative and an antiapoptotic response in renal tubular epithelial cells, these data suggest that VEGF may act as a survival factor for renal tubular epithelium in vivo.

Rational Design of Anti-Angiogenic Peptides to Inhibit VEGF/VEGFR2 Interactions for Cancer Therapeutics

2021 ◽  
Vol 21 ◽  
Author(s):  
Samaneh Ghasemali ◽  
Safar Farajnia ◽  
Abolfazl Barzegar ◽  
Mohammad Rahmati-yamchi ◽  
Babak Negahdari ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Rational Design ◽  
Mutation Screening ◽  
Dynamics Simulation ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Endothelial Growth Factor ◽  
Vegf Signaling Pathway

Background: Angiogenesis is a critical physiological process that plays a key role in tumor progression, metastatic dissemination, and invasion. In the last two decades, the vascular endothelial growth factor (VEGF) signaling pathway has been the area of extensive researches. VEGF executes its special effects by binding to vascular endothelial growth factor receptors (VEGFRs), particularly VEGFR-2. Objective: The inhibition of VEGF/VEGFR2 interaction is known as an effective cancer therapy strategy. The current study pointed to design and model an anti-VEGF peptide based on VEGFR2 binding regions. Method: The large-scale peptide mutation screening was used to achieve a potent peptide with high binding affinity to VEGF for possible application in inhibition of VEGF/VEGFR2 interaction. The AntiCP and Peptide Ranker servers were used to generate the possible peptides library with anticancer activities and prediction of peptides bioactivity. Then, the interaction of VEGF and all library peptides were analyzed using Hex 8.0.0 and ClusPro tools. A number of six peptides with favorable docking scores were achieved. All of the best docking scores of peptides in complexes with VEGF were evaluated to confirm their stability, using molecular dynamics simulation (MD) with the help of the GROMACS software package. Results: As a result, two antiangiogenic peptides with 13 residues of PepA (NGIDFNRDFFLGL) and PepC (NGIDFNRDKFLFL) were achieved and introduced to inhibit VEGF/VEGFR2 interactions. Conclusions: In summary, this study provided new insights into peptide-based therapeutics development for targeting VEGF signaling pathway in tumor cells. PepA and PepC are recommended as potentially promising anticancer agents for further experimental evaluations.

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