Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferationin vitro

Despite developments in assisted reproductive technology, there is immaterial progress in the implantation and pregnancy rates. Intrauterine infusion (IUIF) of autologous platelet-rich plasma (PRP) might renew implantation rates through its paracrine properties by progression cytokines and growth factors which favor implantation. Here we determine whether the IUIF of autologous PRP had a role in pregnancy outcome through its outcome on epidermal growth factor and endometrial thickness. An overall of 43 patients where prospectively randomly dispersed into two groups subjected to a superovulation program using Letrozole® tablet orally 2.5 mg twice daily 12 hours apart from day 2 for 5 days for one cycle. 20 women were considered as control receiving the conventional intrauterine insemination (IUI) management while 23 of them were given PRP by IUIF on the day of human chorionic gonadotrophin injection. The IUI was done for both groups 36-48 hours after confirming ovulation. The blood samples were collected from both groups on the day of IUI for the valuation of epidermal growth factor and an ultrasound was done on the day of human chorionic gonadotrophin injection and day of IUI for assessment of endometrial thickness. The mean endometrial thickness in the PRP group at the day of IUI was significantly thicker than that of the control group and the difference in percentage change of endometrial thickness between PRP group and controls significantly higher in PRP group. The mean epidermal growth factor and the pregnancy rate were significantly superior in the PRP group than that of controls. In conclusion, autologous PRP IUIF was well-tolerated and resulted in a significant expansion in endometrial thickness, epidermal growth factor Level and, subsequent pregnancy rate in an infertile woman undergoing IUI.

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Epidermal growth factor-like repeats of SCUBE1 derived from platelets are critical for thrombus formation

Cardiovascular Research ◽

10.1093/cvr/cvz036 ◽

2019 ◽

Vol 116 (1) ◽

pp. 193-201

Author(s):

Wei-Ju Liao ◽

Meng-Ying Wu ◽

Chen-Chung Peng ◽

Yi-Chung Tung ◽

Ruey-Bing Yang

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Arterial Thrombosis ◽

Platelet Rich Plasma ◽

Thrombus Formation ◽

Critical Role ◽

Adenosine Diphosphate ◽

Genetic Ablation ◽

Epidermal Growth

Abstract Aims SCUBE1 [signal peptide-CUB-epidermal growth factor (EGF) domain-containing protein 1], expressed in endothelial cells (ECs) and platelets, exists in soluble or membrane forms. We previously showed that soluble SCUBE1 is a biomarker for platelet activation and also an active participant of thrombosis. However, whether the adhesive module of its EGF-like repeats is essential and the specific contribution of SCUBE1 synthesized in ECs or platelets to thrombosis in vivo remain unclear. Methods and results We generated new mutant (Δ2) mice lacking the entire EGF-like repeats to evaluate the module’s functional importance during thrombogenesis in vivo. The Δ2 platelet-rich plasma showed markedly impaired platelet aggregation induced by agonists including adenosine diphosphate, collagen, the thrombin agonist PAR-4 peptide and the thromboxane A2 analogue U46619. Consistently, genetic ablation of the EGF-like repeats diminished arterial thrombosis and protected Δ2 mice against lethal thromboembolism. On flow chamber assay, whole blood isolated from Δ2 or wild-type (WT) mice pre-treated with blocking antibodies against the EGF-like repeats showed a significant decrease in platelet deposition and thrombus formation on collagen-coated surfaces under arterial shear rates. Moreover, we created animals expressing SCUBE1 only in ECs (S1-EC) or platelets (S1-PLT) by reciprocal bone-marrow transplantation between WT and Δ2 mice. The time of carotid arterial thrombosis induced by ferric chloride was normal in S1-PLT chimeric mice but much prolonged in S1-EC animals. Conclusions We demonstrate that platelet-derived SCUBE1 plays a critical role in arterial thrombosis via its adhesive EGF-like repeats in vivo and suggest targeting these adhesive motifs of SCUBE1 for potential anti-thrombotic strategy.

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Epidermal growth factor or platelet-rich plasma combined with induced membrane technique in the treatment of segmental femur defects: an experimental study

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-020-02142-2 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Ökkeş Bilal ◽

Duran Topak ◽

Mustafa Kınaş ◽

Ergül Belge Kurutaş ◽

Betül Kızıldağ ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Rat Model ◽

Platelet Rich Plasma ◽

Bone Defects ◽

Control Group ◽

Therapeutic Benefits ◽

Masquelet Technique ◽

Membrane Technique ◽

Epidermal Growth

Abstract Objective Extensive bone defects remain a therapeutic challenge necessitating alternative surgical approaches with better outcomes. Can increase the effectiveness of PRP or EGF treatment in surgical treatment of large bone defects with Masquelet technique? Aim of this study examined potential therapeutic benefits of the Masquelet technique with induced membranes in combination with platelet-rich plasma (PRP) or epidermal growth factor (EGF) in a rat model of segmental femur defect. Methods Three groups each consisting of 20 Sprague-Dawley rats were defined as follows: EGF group, PRP group, and control group. A femoral bone defect was created and filled with antibiotic embedded polymethyl methacrylate. Half of the animals in each group were sacrificed at week 6 and the pseudo-membranes formed were analyzed. In the remaining half, the cement was removed and the space was filled with autograft. After another 6 weeks, the structures formed were examined radiologically, histologically, and biochemically. Results At week 6, both PRP and EGF groups had significantly higher membrane CD31, TGF-beta, and VEGF levels than controls. At week 12, when compared to controls, PRP and EGF groups had significantly higher membrane CD31 levels and the PRP group had significantly higher membrane TGF levels. Regarding bone tissue levels, PRP and EGF groups had significantly higher VEGF levels and the EGF group had significantly higher BMP levels. In addition, PRP and EGF groups had higher radiological scores than controls. However, the two experimental groups did not differ with respect to any parameter tested in this study. Conclusion Both PRP and EGF seem to be associated with histological, biochemical, and radiological improvements in experimental rat model of Masquelet technique, warranting in further clinical studies. Level of evidence Level 5

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Epidermal Growth Factor Receptor Is Not Required for Human Cytomegalovirus Entry or Signaling

Journal of Virology ◽

10.1128/jvi.00169-07 ◽

2007 ◽

Vol 81 (12) ◽

pp. 6241-6247 ◽

Cited By ~ 81

Author(s):

Marisa K. Isaacson ◽

Adam L. Feire ◽

Teresa Compton

Keyword(s):

Epidermal Growth Factor Receptor ◽

Endothelial Cell ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Cell Lines ◽

Virus Entry ◽

Growth Factor Receptor ◽

Negative Cell ◽

Epidermal Growth ◽

Egfr Kinase

ABSTRACT Human cytomegalovirus (HCMV) can bind, fuse, and initiate gene expression in a diverse range of vertebrate cell types. This broad cellular tropism suggests that multiple receptors and/or universally distributed receptors mediate HCMV entry. Our laboratory has recently discovered that certain β1 and β3 integrin heterodimers are critical mediators of HCMV entry into permissive fibroblasts (A. L. Feire, H. Koss, and T. Compton, Proc. Natl. Acad. Sci. USA 101:15470-15475, 2004). It has also been reported that epidermal growth factor receptor (EGFR) is necessary for HCMV-mediated signaling and entry (X. Wang, S. M. Huong, M. L. Chiu, N. Raab-Traub, and E. E. Huang, Nature 424:456-461, 2003). Integrins are known to signal synergistically with growth factor receptors, and this coordination was recently reported for EGFR and β3 integrins in the context of HCMV entry (X. Wang, D. Y. Huang, S. M. Huong, and E. S. Huang, Nat. Med. 11:515-521, 2005). However, EGFR-negative cell lines, such as hematopoietic cells, are known to be infected by HCMV. Therefore, we wished to confirm a role for EGFR in HCMV entry and then examine any interaction between β1 integrins and EGFR during the entry process. Surprisingly, we were unable to detect any role for EGFR in the process of HCMV entry into fibroblast, epithelial, or endothelial cell lines. Additionally, HCMV did not activate the EGFR kinase in fibroblast cell lines. We first examined HCMV entry into two EGFR-positive or -negative cell lines but observed no increase in entry when EGFR was expressed to high levels. Physically blocking EGFR with a neutralizing antibody in fibroblast, epithelial, or endothelial cell lines or blocking EGFR kinase signaling with a chemical inhibitor in fibroblast cells did not inhibit virus entry. Lastly, we were unable to detect phosphorylation of EGFR in fibroblasts cells in response to HCMV stimulation. Our findings demonstrate that EGFR does not play a significant role in HCMV entry or signaling. These results suggest that specific integrin heterodimers either act alone as the primary entry receptors or interact in conjunction with an additional receptor(s), other than EGFR, to facilitate virus entry.

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Epidermal Growth Factor or Platelet Rich Plasma Combined With Induced Membrane Technique in the Treatment of Segmental Femur Defects: An Experimental Study

10.21203/rs.3.rs-84460/v1 ◽

2020 ◽

Author(s):

Ökkeş Bilal ◽

Duran Topak ◽

Mustafa Kınaş ◽

Ergül Belge Kurutaş ◽

Betül Kızıldağ ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Rat Model ◽

Platelet Rich Plasma ◽

Bone Defects ◽

Control Group ◽

Therapeutic Benefits ◽

Masquelet Technique ◽

Membrane Technique ◽

Epidermal Growth

Abstract Objective: Extensive bone defects remain a therapeutic challenge necessitating alternative surgical approaches with better outcomes. Can increase the effectiveness of PRP or EGF treatment in surgical treatment of large bone defects with masquelet technique?Aim of this study examined potential therapeutic benefits of the Masquelet technique with induced membranes in combination with platelet rich plasma (PRP) or epidermal growth factor (EGF) in a rat model of segmental femur defect.Methods: Three groups each consisting of 20 Sprague-Dawley rats were defined as follows: EGF group, PRP group, and control group. A femoral bone defect was created and filled with antibiotic embedded polymethyl metacrylate. Half of the animals in each group were sacrificed at week 6 and the pseudo-membranes formed were analyzed. In the remaining half, the cement was removed and the space was filled with autograft. After another six weeks, the structures formed were examined radiologically, histologically and biochemically.Results: At week 6, both PRP and EGF groups had significantly higher membrane CD31, TGF and VEGF levels than controls. At week 12, when compared to controls, PRP and EGF groups had significantly higher membrane CD31 levels and PRP group had significantly higher membrane TGF levels. Regarding bone tissue levels, PRP and EGF groups had significantly higher VEGF levels and EGF group had significantly higher BMP levels. In addition, PRP and EGF groups had higher radiological scores than controls. However, the two experimental groups did not differ with respect to any parameter tested in this study. Conclusion: Both PRP and EGF seems to be associated with histological, biochemical, and radiological improvements in experimental rat model of Masquelet technique, warranting in further clinical studies.

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A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains.

Molecular and Cellular Biology ◽

10.1128/mcb.12.4.1698 ◽

1992 ◽

Vol 12 (4) ◽

pp. 1698-1707 ◽

Cited By ~ 215

Author(s):

J Partanen ◽

E Armstrong ◽

T P Mäkelä ◽

J Korhonen ◽

M Sandberg ◽

...

Keyword(s):

Endothelial Cell ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Tyrosine Kinase ◽

Cell Lines ◽

Receptor Tyrosine Kinase ◽

Cell Surface Receptor ◽

Endothelial Cell Surface ◽

Surface Receptor ◽

Epidermal Growth

Endothelial cell surfaces play key roles in several important physiological and pathological processes such as blood clotting, angiogenic responses, and inflammation. Here we describe the cloning and characterization of tie, a novel type of human endothelial cell surface receptor tyrosine kinase. The extracellular domain of the predicted tie protein product has an exceptional multidomain structure consisting of a cluster of three epidermal growth factor homology motifs embedded between two immunoglobulinlike loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Additionally, a cDNA form lacking the first of the three epidermal growth factor homology domains was isolated, suggesting that alternative splicing creates different tie-type receptors. Cells transfected with tie cDNA expression vector produce glycosylated polypeptides of 117 kDa which are reactive to antisera raised against the tie carboxy terminus. The tie gene was located in chromosomal region 1p33 to 1p34. Expression of the tie gene appeared to be restricted in some cell lines; large amounts of tie mRNA were detected in endothelial cell lines and in some myeloid leukemia cell lines with erythroid and megakaryoblastoid characteristics. In addition, mRNA in situ studies further indicated the endothelial expression of the tie gene. The tie receptor tyrosine kinase may have evolved for multiple protein-protein interactions, possibly including cell adhesion to the vascular endothelium.

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