DigitalUM :: Browsing by Subject "VEGF"

Browsing by Subject "VEGF"

Now showing 1 - 13 of 13

Open Access
A GFP endometriosis model reveals important morphological characteristics of the angiogenic process that govern benign and malignant diseases
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Machado, Daniel Escorsim; Júnior, Antônio Palumbo; Santos, João Marcos; Mattos, Rômulo Medina; dos Santos, Thiago Alves; Seabra, Sergio Henrique; Boldrini, Leonardo da Cunha; Machado, Jamila Alessandra Perini; Nasciutti, Luiz Eurico
Endometriosis involves the growth of endometriotic tissue outside the uterine cavity, and is frequently associated with different malignancies. A well-reported alteration in the disease microenvironment is the proliferation of new blood vessels around the lesions, as part of a necessary repertory to contribute to the invasiveness and development of infiltrating endometriosis. Therefore, the establishment of a reliable experimental model is essential to elucidate the contribution of angiogenesis and to develop new therapeutic approaches to endometriosis treatment. For this purpose we transplanted endometrial fragments from green fluorescent protein (GFP)-mice (n=20) into the peritoneal cavity of wild-type mice (n=20), and then analyzed the morphological changes and the process of angiogenesis. The lesions were cystic and vascularized, and showed morphological hallmarks such as endometrial glands and stroma. An increase in endometriotic lesion vascular density was revealed by immunostaining and RNAm expression for Vegf and its receptor Flk-1, and the lesions were confirmed as a tissue-donor source by GFP fluorescent cells. The same pattern was observed through staining of activated macrophages and an increase of about 25% in the number of macrophage-positive cells was also demonstrated in endometriotic lesions by flow cytometry, which concords with previous data that correlate endometriosis, angiogenesis and inflammation. According to our understanding, this is the first demonstration that the pattern of the angiogenic process in the GFP endometriosis model is very similar to that of cancer. These observations will be useful for investigation of the process of angiogenesis involved in the attachment and invasion of endometrial cells, as well as an in vivo platform model to study the effects of antiangiogenic drugs.
Open Access
Aberrant expression and association of VEGF and Dll4/Notch pathway molecules under hypoxia in patients with lung cancer
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Yu, Shuang; Sun, Jianhua Sun; Zhang, Jingru; Xu, Xingfang; Li, Hong; Shan, Baozhong; Tian, Tian; Wang, Hongchun; Ma, Daoxin; Ji, Chunyan
Tumor angiogenesis plays important roles in the pathogenesis and prognosis of lung cancer. Both vascular endothelial growth factor (VEGF) and Dll4/Notch pathways are critical for angiogenesis, whereas their relationship under hypoxia in lung cancer remains unknown. Thus, in the present study, we evaluated the expression of VEGF and Dll4/Notch signaling molecules, and assessed their association with the microvessel density (CD31) and hypoxia (HIF1a) in lung cancer and normal lung tissues using immunohistochemical and Real-time RT-PCR techniques. Then, we investigated the biological function of Dll4 by transfecting Dll4 into HUVECs. In lung cancer tissues, Notch pathway molecules (HES1) and VEGF pathway molecules (VEGFR1 and VEGFR2) were significantly up-regulated, while the ratio of VEGFR1/VEGFR2 was decreased. CD31 and HIF1a were also found to be elevated in lung cancer. VEGFR1 was negatively correlated with Notch1 while positively correlated with Dll4. CD31 was positively correlated with HIF1a but negatively correlated with VEGFR1. Moreover, HIF1a was nearly positively correlated with HES1 in lung cancer tissues. After transfection, Dll4, Notch1 and VEGFR1 were up-regulated while VEGF and VEGFR2 were down-regulated in Dll4-transfected HUVECs compared with controls. Also, our findings suggest that the expression of VEGF and VEGFR2 increased gradually with the disease progression of lung cancer. In summary, VEGF and Notch signaling pathway molecules were overexpressed in lung cancer, which positively correlates with hypoxia (HIF1a) and angiogenesis (CD31). There might be a negative feedback loop between VEGF and Dll4/Notch signaling pathway in lung tumor angiogenesis.
Open Access
Appearance of vascular endothelial growth factor (VEGF) in femoral head in the growing rat
(Murcia : F. Hernández, 2001) Ichigatani, M.; Saga, T.; Yamaki, K.; Yoshizuka, M.
In this study, we examined the appearance of vascular endothelial growth factor (VEGF) in the femoral head of the growing rat using an immunocytochemical technique. Our results showed VEGF-immunopositive cells existed in the inner region and peripheral region of the femoral head at each developmental stage. In the 19-day-old fetus, immunopositive mesenchymal cells were demonstrated in the peripheral region of the femoral head. At 1 to 10 days after birth, VEGF immunoreactivities were observed in the osteoblasts, osteoclasts, periosteum, perichondrium and cartilage matrix of the femur. At 15 days after birth, VEGF immunoreactive chondrocytes appeared in the apex area of the femoral head. In this stage, the femoral head is still constituted by chondrocytes and no apparent vascular formation has been observed. Thereafter, the immunopositive chondrocytes in the femoral head increased in number. The penetration of capillaries was recognized within the ligament of the femoral head at 60 days after birth. The results indicate that some chondrocytes in the femoral head produce VEGF before the beginning of ossification, and that VEGF may play an important role in the penetration of blood vessels into the femoral head from the ligament of the femoral head.
Open Access
Differential expression of HIF-1α and its hypoxia-related inducers in the spleens of plateau yaks and plain yellow cattle
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhou, Manlin; Dong, Shihui; Wang, Jun; Luo, Xuehui; Li, Rui; Zhang, Yiyang; Ding, Haie; Tan, Xiao; Qiao, Zilin; Yang, Kun; Chen, Weiji
The present study aims to investigate the distribution and expression characteristics of HIF-1α, VEGF, VEGFR-2, VCAM-1, and IL-4 in the spleen of plateau yaks and plain yellow cattle and to speculate the possible regulatory role of HIF-1α and its related hypoxia-inducible factors in the adaptation of the yak spleen to the plateau hypoxic environment. Histological features were observed using H&E and PAS stains. Immunohistochemical staining and optical density analysis were applied to investigate the distribution and differences in the expression of HIF-1α, VEGF, VEGFR-2, VCAM-1, and IL-4 in the spleen of yaks and cattle. The results showed that the area of splenic trabeculae and splenic nodules was significantly larger in the yak than in yellow cattle (P<0.05). Glycogen was mainly distributed in splenic arterial endothelial cells, vascular smooth muscle cells, splenic blood sinusoidal endothelial cells, and fibroblasts, and the distribution was significantly higher in the spleen of yaks than in cattle (P<0.05). HIF-1α, VEGF, VEGFR-2, VCAM-1, and IL-4 were mainly expressed in lymphocytes, arterial endothelial cells, vascular smooth muscle cells, splenic blood sinusoidal endothelial cells, and fibroblast cytoplasm, with higher expression in yak spleen (P<0.05). In conclusion, combining the differences in spleen tissue structure, glycogen distribution, and expression distribution of several hypoxia-related factors between yaks and cattle, we suggest that HIF-1α, VEGF, VEGFR-2, VCAM-1, and IL-4 may be important factors in the adaptation of yak spleen to the plateau environment, which provides a theoretical basis for further exploring the adaptation mechanism of plateau hypoxia in yaks.
Open Access
Effect of diabetes blood-stasis syndrome and Xuefu Zhuyu decoction on ERK1/2-VEGF signal pathway in rat retina Müller cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Ye, Xiaofeng; Ren, Hui; Jiang, Tingting; Zhang, Ting; Li, Gang
Aims. This research was aimed to investigate whether diabetic blood-stasis syndrome had a relationship with ERK1/2-VEGF signaling pathway in rat retina Müller cells and Traditional Chinese Drugs designed for promoting blood circulation to remove blood stasis had effectiveness for diabetic retinopathy (DR) treatment. Methods. Immunofluorescence was applied to determine purity of Müller cells. Müller cells were stimulated by blood serum obtained from rats with blood-stasis syndrome and then treated by Xuefu Zhuyu decoction. Western blot analysis, RT-PCR and ELISA were used to measure the expression of VEGF. Western blot analysis was used to determine the phosphorylation of ERK1/2. The status of AP-1 DNA binding activity was monitored by electrophoretic mobility shift assay (EMSA). Results. Stimulation of Müller cells by blood serum of rat with diabetic blood stasis increased the secretion of VEGF, activated ERK1/2 and AP-1 DNA-binding activity. And treatment of Xuefu Zhuyu decoction could weaken this phenomenon. What's more, ERK1/2 signaling pathway inhibitor U0126 also could inhibit the expression of VEGF. Conclusions. Diabetic blood-stasis syndrome in theory of traditional Chinese Medicine has positive role in regulating ERK1/2-VEGF signaling pathway. Traditional Chinese drugs for promoting blood circulation to remove blood stasis would be an effective therapy to treat DR.
Open Access
Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Valladares, Macarena; Plaza Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen
Introduction: Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. Objective: To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Methodology: Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. Results: In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Conclusions: Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.
Open Access
Elevated blood/lymphatic vessel ratio in pterygium and its relationship with vascular endothelial growth factor (VEGF) distribution
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Martín López, Javier; Pérez Rico, Consuelo; García Honduvilla, Natalio; Buján, Julia; Pascual, Gemma
Introduction. Pterygium is a conjunctival fibrovascular tissue growth on the cornea. The pathogenesis of pterygium involves several factors such as the presence of active angiogenic factors. Expansion of the lymphatic microvasculature has also been hypothesized. This study examines the activity of the angiogenic/lymphangiogenic factor VEGF and the expression of vascular and lymphatic endothelial proteins in pterygia and normal conjunctival tissues. Materials and methods. Primary grade 2 pterygium (n=20) and normal conjunctiva (n=20) biopsies were obtained during surgery after written informed consent. mRNA expression for CD31, podoplanin, and VEGF (isoforms VEGF-A and VEGF-165) were determined by qRT-PCR. Tissue samples were also processed for immunohistochemical techniques to examine the lymphatic and vascular endothelium (anti-D2-40, antiCD31 respectively) and VEGF-A and VEGF-C levels and distribution. Results. VEGF-A gene expression levels failed to differ between the healthy and pterygium tissues. However, expression of its more angiogenic isoform, VEGF-165, was significantly higher in the pterygia. Immunohistochemistry revealed the greater presence of VEGF-A, compared to VEGF-C, in pterygium than conjunctiva, both in blood vessels and extracellular matrix. In addition, pterygia showed higher expression levels of the endothelial junction protein CD31. Lymphatic marker D2-40 expression was slightly augmented in this pathological tissue. The ratio between blood and lymphatic vessel counts was 1.05 in the normal conjunctiva and 3-fold this value in pterygium. Conclusion. In pterygium, while both lymphangiogenesis and angiogenesis take place, the formation of new blood vessels is the most relevant event, correlating with the increased expression of vascular endothelial CD31 and an elevated blood/lymphatic vessel ratio. The presence of high levels of VEGF-A in both vessel networks and extracellular matrix in human pterygium tissue may have a major impact on angiogenesis in this pathological tissue
Metadata only
Follicle-stimulating hormone promotes nerve growth factor and vascular endothelial growth factor expression in epithelial ovarian cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Garrido, Maritza P.; Bruneau, Nicole; Vega, Margarita; Selman, Alberto; Tapia, Julio C.; Romero, Carmen
Ovarian cancer is the first cause of death for gynecological malignances in developed countries and around 80% correspond to Epithelial Ovarian Cancer (EOC). Overexpression of Nerve Growth Factor (NGF) and its high affinity receptor TRKA are involved in EOC progression, modulating several oncogenic processes such as angiogenesis by the increase of Vascular Endothelial Growth Factor (VEGF). FSH receptors (FSH-R) are present in EOC, but their changes and contribution during EOC progression are still not thoroughly known. The aims of this study were to evaluate the abundance of FSH receptors during EOC differentiation and to determine whether FSH modulates oncoproteins such as NGF and VEGF in ovarian cells. FSH-R expression in EOC tissues and cell lines (A2780, poorly differentiated EOC cells and HOSE, non-tumoral ovarian surface epithelial cells) were measured by RT- PCR and laser capture of epithelial cells from EOC samples by qPCR. FSH-R protein levels were evaluated by immunohisto/cytochemistry. Additionally, ovarian explants and ovarian cell lines were stimulated with FSH and/or FSH-R inhibitor to assess NGF and VEGF mRNA and protein levels. The results showed that FSH-R levels decreased during loss of EOC cell differentiation, nevertheless these receptors are still present in poorly differentiated EOC. FSH increased NGF expression in ovarian cells, which was prevented using a FSH-R inhibitor. Similarly, in ovarian cancer explants, FSH increased NGF and VEGF mRNA, as well as NGF protein levels. These results suggest that FSH would display a key role not only in initial stages of EOC, but also in late stages of this disease, by modulation of NGF and VEGF levels in EOC cells
Open Access
Iodine deficiency induces a VEGF-dependent microvascular response in salivary glands and in the stomach
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Vanderstraeten, Jessica; Derradji, Hanane; Craps, Julie; Sonveaux, Pierre; Colin, Ides M.; Many, Marie Christine; Gérard, Anne Catherine
Despite efforts to optimize iodine supply in iodine deficient countries, iodine deficiency (ID) remains a global problem worldwide. Activation of the local microvasculature by ID in the thyroid gland aims at improving the local supply of iodide. For this purpose, the thyrocytes secrete vascular endothelial growth factor (VEGF) that acts on adjacent capillaries, via a reactive oxygen species (ROS)/Hypoxia Inducible factor (HIF)- dependent pathway. Beside the thyroid, other organs including salivary glands and the stomach do express the sodium/iodide symporter (NIS) and are able to take iodide up, potentially rendering them sensitive to ID. To verify this hypothesis, ID-induced effects on the local microvasculature were studied in salivary glands and in the stomach. ID was induced by feeding young mice with an iodide-deficient diet and NIS inhibitor perchlorate in the drinking water. In salivary glands, ID induced a transient increase in HIF-1α protein expression accompanied by a transient, VEGFdependent increase in blood flow. In the gastric mucosa, ID transiently increased VEGF expression in the mucinsecreting epithelium and in ghrelin-secreting endocrine cells. These observations suggest that microvascular changes in response to ID occur in NIS-expressing tissues other than the thyroid. NIS expressing cells could be viewed as iodide sensors that respond to ID by inducing vascular changes, probably to optimize iodide bioavailability at regional or systemic levels.
Open Access
Isoflurane post-conditioning stimulates the proliferative phase of myocardial recovery in an ischemia-reperfusion model of heart injury in rats
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Agnić, Ivan; Vukojevic, Katarina; Saraga-Babić, Mirna; Filipović, Natalija; Grković, Ivica
Summary. The application of isoflurane in a postconditioning manner, during early reperfusion following a period of coronary occlusion, has numerous beneficial effects on the ischemic myocardium, including reduction of infarct size. It does so by stimulating a sequence of well studied anti-apoptotic pro-survival mechanisms in a similar manner to various ‘ischemic’ pre-/postconditioning approaches which achieve their cardio protective effects in both laboratory and clinical situations. Proliferation of newly formed blood vessels, resulting in formation of highly vascularized granulation tissue, is an essential stage of infarct healing. It can be evaluated by detecting various angiogenic factors, including vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) or by quantification of expression of vascular smooth muscle progenitors, such as Nestin. Expression of these three markers was used to evaluate the effect of early isoflurane post-conditioning in ischemia-reperfusion type cardiac injury. A large reduction in infarct size (59.3% of control), and marked increase of expression of VEGF (43.4%), PECAM1/CD31 (136%) and Nestin (77.9%) was found in experimental animals when compared to control animals that did not receive isoflurane treatment. Hence, based on our results, we can emphasize two morphologically detectable benefits of isoflurane post-conditioning: a marked reduction in infarct size and much better organization/vascularization of necrotic tissue.
Open Access
Quantitative immunohistochemical assessment of blood and lymphatic microcirculation in cutaneous lichen planus lesions
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Výbohová, Desanka; Mellová, Yvetta; Adamicová, Katarína; Adamkov, Marián; Hešková, Gabriela
Latest advances have brought to light the hypothesis that angiogenesis and lymphangiogenesis are tightly connected to some chronic inflammatory diseases. The present study focuses on immunohistochemical assessment of the quantitative changes in the blood and lymphatic microcirculatory bed in common chronic dermatosis - cutaneous lichen planus. Double immunohistochemistry with CD34 and podoplanin antibodies was used to detect blood and lymphatic endothelium, while anti-human VEGF was used for the observation of a key angiogenesis and lymphangiogenesis inducer. Morphometric analysis was performed with QuickPhoto Micro image analysis software. Results confirmed statistically significant enlargement of both the blood and lymphatic microcirculatory beds. Compared to healthy skin, cutaneous lichen planus lesions revealed 1.6 times enlarged blood microcirculatory bed and 1.8 times enlarged lymphatic microcirculatory bed. Vascular endothelial growth factor (VEGF) expression in lesional skin was significantly higher in the epidermis (19.1 times increase) than in the dermis (10.3 times increase). These findings indicate a tight association of angiogenesis and lymphangiogenesis with the pathogenesis of cutaneous lichen planus.
Open Access
TIMP-1 promotes VEGF-induced neovascularization in the retina
(Murcia : F. Hernández, 2001) Yamada, E.; Tobe, T.; Yamada, H.; Okamoto, N.; Zack, D.J.; Werb, Z.; Soloway, P.D.; Campochiaro, P.A.
Proteolysis of vascular basement membranes and surrounding extracellular matrix is a critica1 early step in neovascularization. It requires alteration of the balance between matrix metalloproteinases (MMPs) and proteins that bind to and inactivate MMPs, tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 has been demonstrated to inhibit neovascularization in chick chorioallantoic membranes. However, TIMP-1 has also been shown to either promote or inhibit cell proliferation and migration in different settings. To determine whether genetic alteration of the MMPDIMP-1 ratio would alter retinal neovascularization, we crossed mice that express vascular endothelial growth factor (VEGF) in photoreceptors with TIMP-1-deficient mice or mice that overexpress TIMP-1. Compared to VEGF transgenepositive/ TIMP-1-sufficient mice, VEGF transgenepositive1TIMP- 1-deficient mice showed smaller neovascular lesions. There was also no difference between the two groups of mice in the appearance of the neovascularization by light or electron microscopy. Compound VEGFITIMP-1 transgenic mice had increased expression of both VEGF and TIMP-1 in the retina, and had more neovascularization than mice that had increased expression of VEGF alone. These gainand loss-of-function data suggest that alteration of the TIMP-1MMP ratio modulates retinal neovascularization in a complex manner and not simply by altering the proteolytic activity and thereby invasiveness of endothelial cells.
Open Access
VEGF-A/VEGF-B/VEGF-C expressions in non- hereditary, non-metastatic phaeochromocytoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Abe, Ichiro; Islam, Farhadul; Lo, Chung Yau; Liew, Victor; Pillai, Suja; Lam, Alfred K.
. Vascular endothelial growth factor (VEGF) is important in pathogenesis of different cancers. The aim of this study is to investigate the relationships between different VEGFs and clinicopathological factors in patients with phaeochromocytomas. Twenty patients (10 men; 10 women) with non-hereditary, non-metastatic phaeochromocytomas were examined for VEGF mRNA expressions by polymerase chain reaction. The expressions were correlated with the clinical and pathological factors of the patients. In addition, mouse double minute 2 (MDM2) expression in these tumours were studied by immunohistochemistry. High expressions of VEGF-A, VEGF-B, and VEGF-C mRNA were detected in 11 (55%), 9 (45%), and 9 (45%) of the tumours respectively. High expression of VEGF-A in phaeochromocytomas was significantly correlated with the tumour size (p=0.025) but did not correlate with patients' age, gender, and tumour laterality. Besides, there was a trend of VEGF-A expression correlated with MDM2 expression (p=0.064). On the other hand, expressions of VEGF-B and VEGF-C were not significantly correlated with tumour size, patients' age, gender, tumour laterality, and MDM2 expression. In addition, high expressions of VEGF-B and VEGF-A were associated with increase of tumour size (p=0.042). Co-expression of different VEGFs did not correlate with MDM2 expression. To conclude, there is a role for VEGF-A/VEGF-B/VEGF-C in the pathogenesis of nonhereditary, non-metastatic phaeochromocytomas.

Browsing by Subject "VEGF"

Results Per Page

Sort Options