scholarly journals Vascular endothelial growth factor-C: its unrevealed role in fibrogenesis

2014 ◽  
Vol 306 (6) ◽  
pp. H789-H796 ◽  
Author(s):  
Tieqiang Zhao ◽  
Wenyuan Zhao ◽  
Weixin Meng ◽  
Chang Liu ◽  
Yuanjian Chen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Type I ◽  
Vascular Endothelial ◽  
Factor C ◽  
Endothelial Growth Factor ◽  
Tgf Β1

Vascular endothelial growth factor (VEGF)-C is a key mediator of lymphangiogenesis. Our recent study shows that VEGF-C/VEGF receptors (VEGFR)-3 are significantly increased in the infarcted rat myocardium, where VEGFR-3 is expressed not only in lymph ducts but also in myofibroblasts, indicating that VEGF-C has an unrevealed role in fibrogenesis during cardiac repair. The current study is to explore the regulation and molecular mechanisms of VEGF-C in fibrogenesis. The potential regulation of VEGF-C on myofibroblast differentiation/growth/migration, collagen degradation/synthesis, and transforming growth factor (TGF)-β and ERK pathways was detected in cultured cardiac myofibroblasts. Our results showed that VEGF-C significantly increased myofibroblast proliferation, migration, and type I/III collagen production. Matrix metalloproteinase (MMP)-2 and -9 were significantly elevated in the medium of VEGF-C-treated cells, coincident with increased tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Furthermore, VEGF-C activated the TGF-β1 pathway and ERK phosphorylation, which was significantly suppressed by TGF-β or ERK blockade. This is the first study indicating that in addition to lymphangiogenesis, VEGF-C is also involved in fibrogenesis through stimulation of myofibroblast proliferation, migration, and collagen synthesis, via activation of the TGF-β1 and ERK pathways.

scholarly journals Estrogen-Induced CCN1 Is Critical for Establishment of Endometriosis-Like Lesions in Mice

2014 ◽  
Vol 28 (12) ◽  
pp. 1934-1947 ◽  
Author(s):  
Yuechao Zhao ◽  
Quanxi Li ◽  
Benita S. Katzenellenbogen ◽  
Lester F. Lau ◽  
Robert N. Taylor ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Tissue Growth ◽  
Endometrial Tissue ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Factor C ◽  
Endothelial Growth Factor

Endometriosis is a prevalent gynecological disorder in which endometrial tissue proliferates in extrauterine sites, such as the peritoneal cavity, eventually giving rise to painful, invasive lesions. Dysregulated estradiol (E) signaling has been implicated in this condition. However, the molecular mechanisms that operate downstream of E in the ectopic endometrial tissue are unknown. To investigate these mechanisms, we used a mouse model of endometriosis. Endometrial tissue from donor mice was surgically transplanted on the peritoneal surface of immunocompetent syngeneic recipient mice, leading to the establishment of cystic endometriosis-like lesions. Our studies revealed that treatment with E led to an approximately 3-fold increase in the lesion size within a week of transplantation. E also caused a concomitant stimulation in the expression of connective tissue growth factor/Cyr61/Nov (CCN1), a secreted cysteine-rich matricellular protein, in the lesions. Interestingly, CCN1 is highly expressed in human ectopic endometriotic lesions. To address its role in endometriosis, endometrial tissue from Ccn1-null donor mice was transplanted in wild-type recipient mice. The resulting ectopic lesions were reduced up to 75% in size compared with wild-type lesions due to diminished cell proliferation and cyst formation. Notably, loss of CCN1 also disrupted the development of vascular networks in the ectopic lesions and reduced the expression of several angiogenic factors, such as vascular endothelial growth factor-A and vascular endothelial growth factor-C. These results suggest that CCN1, acting downstream of E, critically controls cell proliferation and neovascularization, which support the growth and survival of endometriotic tissue at ectopic sites. Blockade of CCN1 signaling during the early stages of lesion establishment may provide a therapeutic avenue to control endometriosis.

scholarly journals Effect of Anesthetic Technique on Serum Vascular Endothelial Growth Factor C and Transforming Growth Factor β in Women Undergoing Anesthesia and Surgery for Breast Cancer

2010 ◽  
Vol 113 (5) ◽  
pp. 1118-1125 ◽  
Author(s):  
Micheal Looney ◽  
Peter Doran ◽  
Donal J. Buggy
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Primary Breast Cancer ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Vascular Endothelial ◽  
Postoperative Change ◽  
Factor C ◽  
Endothelial Growth Factor

Background In breast cancer, vascular endothelial growth factor C, transforming growth factor β, placental growth factor, and fibroblast growth factor (acidic and basic) promote angiogenesis and metastases. We tested the hypothesis that a propofol-paravertebral anesthetic (PPA) technique would attenuate postoperative changes in these angiogenic factors to a greater extent than balanced general anesthesia (GA) and morphine analgesia in women undergoing surgery for primary breast cancer. Method Forty women with primary breast cancer undergoing surgical excision were randomized to receive either standard GA or PPA technique. Venous blood was sampled before and at 24 h after surgery and serum analyzed. The primary endpoint was a preoperative versus postoperative change in vascular endothelial growth factor C and transforming growth factor β concentrations. Results Using a visual analog scale (median [25-75% interquartile range]), PPA patients (1 [0-2]) had less pain at 2 h (P = 0.02) than did GA patients (3 [2-5]). The mean postoperative change in vascular endothelial growth factor C concentrations among GA patients was 733 versus 27 pg/ml for PPA patients (difference, 706 [97.5% CI, 280-1,130] pg/ml, P = 0.001). In contrast, the mean postoperative change in transforming growth factor β concentration among GA patients was -163 versus 146 pg/ml for PPA patients (difference, 309 [97.5% CI, -474 to -143] pg/ml, P = 0.005). Concentrations of placental growth factor and fibroblast growth factor, both acidic and basic, were undetectable in serum. Conclusion Anesthetic technique influences serum concentrations of factors associated with angiogenesis in primary breast cancer surgery.

scholarly journals THE STUDY OF THE ASSOCIATION OF SINGLE-NUCLEOTIDE POLYMORPHISMS ARG25PRO OF THE TRANSFORMING GROWTH FACTOR Β1 GENE AND C634G OF THE VASCULAR ENDOTHELIAL GROWTH FACTOR GENE WITH THE RISK OF ATOPIC DERMATITIS IN CHILDREN

2017 ◽  
Vol 14 (4-5) ◽  
pp. 66-70
Author(s):  
A A Lebedenko ◽  
T P Shkurat ◽  
E V Mashkina ◽  
O E Semernik ◽  
T K Dreyzina
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Atopic Dermatitis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Control Group ◽  
Vascular Endothelial ◽  
Nucleotide Polymorphisms ◽  
Endothelial Growth Factor ◽  
Vegfa Gene ◽  
Tgf Β1

The growth factors such as transforming growth factor β (TGF-β) and vascular endothelial growth factor (VEGF) are played a particular role in the pathogenesis of atopic dermatitis. Therefore, the study of the genetic aspects of their association with risk of atopic dermatitis development in children is of great practical and scientific interest. Background. To study the association of the Arg25Pro polymorphisms of the TGF-β gene and the C634G gene of the VEGF gene with the risk of atopic dermatitis in children. Methods. Allelic variants of Arg25Pro gene TGF-β1 and S634G VEGFA gene in children with atopic dermatitis were studied with method of allelespecific polymerase chain reaction. The control group consisted of patients I and Ila of the health groups of the corresponding sex and age. Results. The results of genetic studies have shown that the occurrence frequency of genotype polymorphism Arg25Pro TGF-β1 gene in patients did not have significant differences from control group (p>0,05). Moreover, among patients who are heterozygous for the gene Arg25Pro TGF-β1, significantly more often had moderate (77,78%) and severe (33,33%) of course of the disease. It is established that the relationship between inheritance of C and Gallele polymorphism C634G VEGFA gene and the development of atopic dermatitis is also statistically significant (χ2=0,33, p=0,57). Conclusion. The study of polymorphisms of Arg25Pro gene of TGF-β and C634G gene of VEGF did not reveal a significant relationship between their inheritance and development of atopic dermatitis in children.

scholarly journals Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling †

Cells ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 142 ◽  
Author(s):  
Flaminia Chellini ◽  
Alessia Tani ◽  
Larissa Vallone ◽  
Daniele Nosi ◽  
Paola Pavan ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
The Impact ◽  
Tgf Β1

The antifibrotic potential of platelet-rich plasma (PRP) is controversial. This study examined the effects of PRP on in vitro transforming growth factor (TGF)-β1-induced differentiation of fibroblasts into myofibroblasts, the main drivers of fibrosis, and the involvement of vascular endothelial growth factor (VEGF)-A in mediating PRP-induced responses. The impact of PRP alone on fibroblast differentiation was also assessed. Myofibroblastic phenotype was evaluated by confocal fluorescence microscopy and western blotting analyses of α-smooth muscle actin (sma) and type-1 collagen expression, vinculin-rich focal adhesion clustering, and stress fiber assembly. Notch-1, connexin 43, and VEGF-A expression were also analyzed by RT-PCR. PRP negatively regulated fibroblast-myofibroblast transition via VEGF-A/VEGF receptor (VEGFR)-1-mediated inhibition of TGF-β1/Smad3 signaling. Indeed TGF-β1/PRP co-treated fibroblasts showed a robust attenuation of the myofibroblastic phenotype concomitant with a decrease of Smad3 expression levels. The VEGFR-1 inhibition by KRN633 or blocking antibodies, or VEGF-A neutralization in these cells prevented the PRP-promoted effects. Moreover PRP abrogated the TGF-β1-induced reduction of VEGF-A and VEGFR-1 cell expression. The role of VEGF-A signaling in counteracting myofibroblast generation was confirmed by cell treatment with soluble VEGF-A. PRP as single treatment did not induce fibroblast myodifferentiation. This study provides new insights into cellular and molecular mechanisms underpinning PRP antifibrotic action.

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