Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas

2015 ◽  
Vol 53 (9) ◽  
Author(s):  
Porfyrios Korompelis ◽  
Christina Piperi ◽  
Christos Adamopoulos ◽  
Georgia Dalagiorgou ◽  
Penelope Korkolopoulou ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Uterine Leiomyomas ◽  
Angiogenic Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Protein Levels ◽  
Cellular Hypertrophy ◽  
Tissue Specimens ◽  
And Control

AbstractLeiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas.Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immunohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography.Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p<0.001, p=0.004, p=0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p=0.021) as well as MMP-9 (p=0.001) peripheral levels in the patient’s group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues.This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance.

scholarly journals Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Xi Guo ◽  
Hong Yi ◽  
Tin Chiu Li ◽  
Yu Wang ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Critical Role ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Underlying Mechanisms ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.

ACTH depletion represses vascular endothelial-cadherin transcription in mouse adrenal endothelium in vivo

2005 ◽  
Vol 34 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Philippe Huber ◽  
Christine Mallet ◽  
Elodie Faure ◽  
Christine Rampon ◽  
Marie-Hélène Prandini ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial ◽  
Flow Cytometry Analysis ◽  
Adhesion Protein ◽  
Adrenal Cells ◽  
Protein Levels ◽  
Vascular Endothelial Cadherin ◽  
Complex Architecture

Vascular endothelial-cadherin (VE-cadherin) is an endothelial cell-specific adhesion protein that is localised at cell–cell contacts. This molecule is an important determinant of vascular architecture and endothelial cell survival. In the adrenal cortex, steroidogenic and endothelial cells form a complex architecture. The adrenocorticotrophin hormone (ACTH) regulates gland homeostasis whose secretion is subjected to a negative feedback by adrenocorticosteroids. The aim of the present study was to determine whether VE-cadherin expression in the adrenal gland was regulated by hormonal challenge. We demonstrated that VE-cadherin protein levels were dramatically decreased (23.5 ± 3.7%) by dexamethasone injections in the mouse and were restored by ACTH within 7 days (94.9 ± 18.6%). Flow cytometry analysis of adrenal cells showed that the ratios of endothelial versus total adrenal cells were identical (35%) in dexamethasone- or ACTH-treated or untreated mice, suggesting that VE-cadherin expression could be regulated by ACTH. We demonstrate the existence of a transcriptional regulation of the VE-cadherin gene using transgenic mice carrying the chloramphenicol acetyl transferase gene under the control of the VE-cadherin promoter. Indeed, the promoter activity in the adrenals, but not in the lung or liver, was decreased in response to dexamethasone treatment (40 ± 1.3%) and was partially restored after gland regeneration by ACTH injection (82 ± 3%). In conclusion, our results show that transcription of a specific endothelial gene is controlled by the hypothalamo–pituitary axis and the data expand the knowledge regarding the role of ACTH in the regulation of the adrenal vascular network.

scholarly journals Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1599-1601 ◽  
Author(s):  
Yoshiyasu Aoki ◽  
Robert Yarchoan ◽  
James Braun ◽  
Aikichi Iwamoto ◽  
Giovanna Tosato
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Human Immunodeficiency Virus ◽  
Potential Role ◽  
Kaposi Sarcoma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Immunodeficiency Virus ◽  
Endothelial Growth Factor ◽  
Primary Effusion Lymphomas

Abstract Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked immunosorbent assay was developed for vIL-6 and applied to the study of PEL. Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL), it was not detectable in any of the control effusions. As expected, all PEL effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have previously been shown to induce vascular endothelial growth factor, which in turn can increase vascular permeability. The results of the current study suggest that these cytokines play a central role in the pathogenesis and manifestations of PEL.

scholarly journals Effect of continuous compressive force on the expression of RANKL, OPG, and VEGF in MC3T3-E1 and MLO-Y4 cells

2018 ◽  
Author(s):  
Yuka Yashima ◽  
Masato Kaku ◽  
Taeko Yamamoto ◽  
Jin Izumino ◽  
Haruka Kagawa ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Compressive Force ◽  
Cell Types ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Key Factors ◽  
Protein Levels ◽  
Gene And Protein Expression ◽  
Receptor Activator ◽  
Endothelial Growth Factor

AbstractOsteocytes, known to have mechano-sensory functions, influence the regulation of bone remodeling. However, the mechanism by which osteocytes regulate bone metabolism when mechanical forces are being applied is still unclear. Osteoclastogenesis is mainly regulated by receptor activator of nuclear factor kappa-B ligand (RANKL); the protein osteoprotegerin (OPG) and angiogenesis also play important roles in osteogenesis. RANKL, OPG, and vascular endothelial growth factor (VEGF) are thought to be key factors for bone metabolism. In this study, we examined the effect of a continuous compressive force (CF) on the expression of RANKL, OPG, and VEGF in osteoblastic murine osteocytes (MLO-Y4) and osteoblastic (MC3T3-E1) cells. Gene and protein expression levels of RANKL, OPG, and VEGF in MLO-Y4 and MC3T3-E1 cells were quantitatively determined by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Both cell types were also subjected to a CF of 1.0 g/cm2 for 1, 3, 6, and 12 hours. Furthermore, the effect of a stretch-activated (S-A) channel was examined by gadolinium (Gd3+) administration. The ratio of gene and protein expressions of RANKL, VEGF, and RANKL/OPG in MLO-Y4 cells were significantly higher than in MC3T3-E1 cells, while the expression of OPG was significantly lower. After CF application, both cell types showed significant increases in RANKL and VEGF expression as well as the RANKL/OPG ratio. Additionally, the upregulated gene and protein levels of these factors were reduced by Gd3+ administration.These findings suggest that osteocytes play more important roles in bone metabolism and angiogenesis than osteoblasts. Osteocytes regulate the expression of RANKL, OPG, and VEGF via the S-A channel through the response to mechanical stress.

scholarly journals LRIG1 Expression and Colorectal Cancer Prognosis

2020 ◽  
Author(s):  
Maryam Bakherad ◽  
Mahdieh Salimi ◽  
Seyed Abdolhamid Angaji ◽  
Frouzandeh Mahjoubi ◽  
Tayebeh Majidizadeh
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Cancer Prognosis ◽  
Protein Levels ◽  
Tumor Tissues ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Leucine Rich Repeats ◽  
And Control

Abstract BackgroundTo make the right treatment decisions about colorectal cancer (CRC) patients reliable predictive and prognostic data are needed. However, in many cases this data is not enough. Some studies suggest that LRIG1 gene (leucine-rich repeats and immunoglobulin-like domains1) has prognostic implications in different kinds of cancers. MethodsOne hundred and two patients with colorectal cancer were retrospectively analyzed for LRIG1 expression at both mRNA and protein levels. SYBR Green Real-Time RT-PCR technique was used for mRNA expression analyses and Glyceraldehyde-3-Phosphate Dehydrogenase gene (GAPDH) was considered as a reference gene for data normalization. LRIG1 protein expression was analyzed using Immunohistochemistry (IHC). Additionally, appropriate statistic analyses were used to assess the expression of LRIG1 in test and control groups. The prognostic significance of LRIG1 expression was analyzed using the univariate and multivariate analyses.ResultsThe data revealed that the expression of LRIG1 in both mRNA and protein levels was down regulated in colorectal tumor tissues (P<0.01) but is not clinically relevant prognostic indicator in CRC. ConclusionsTherefore, it is suggested that LRIG1 expression analyses may not be considered as an important issue when making informed and individualized clinical decisions regarding the management of colorectal cancer patients.

scholarly journals Genetic polymorphisms of Vascular Endothelial Growth Factor (VEGF) associated with endometriosis in Nigerian women

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ochuwa Adiketu Babah ◽  
Oyesola Oyewole Ojewunmi ◽  
Akinniyi Adediran Osuntoki ◽  
Melissa A. Simon ◽  
Bosede Bukola Afolabi
Keyword(s):  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Nucleotide Polymorphisms ◽  
Nigerian Women ◽  
Pcr Rflp ◽  
Hardy Weinberg Equilibrium ◽  
Elisa Technique ◽  
Genomic Dnas ◽  
And Control ◽  
Endothelial Growth Factor

Abstract Objective To determine if genetic polymorphism of VEGF is associated with the development of endometriosis in Nigerian women. Study design Case control study of 100 women (50 healthy controls and 50 with endometriosis). Serum VEGF concentration of participants were determined using enzyme-linked immunosorbent assay (ELISA) technique. Genomic DNAs were isolated from peripheral blood samples and quantified by nanodrop spectrophotometer one. Single nucleotide polymorphisms genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP). Results Mean age of participants was 32.96 ± 6.91 years for control and 32.04 ± 7.56 years for cases. VEGF levels in case and control groups were not statistically different (82.68 pg/ml [69.11–121.11 pg/ml] vs. 82.81 pg/ml [72.90–113.82 pg/ml] respectively; p = 0.967). All four genotypes examined were in Hardy–Weinberg equilibrium. Minor allele frequency of − 460T > C, − 1154G > A, + 936C > T and + 2578C > A were 24%, 8%, 6% and 10% in the control and 19%, 9%, 5% and 14% in endometriosis patients. However, allele and genotype distributions of − 460T > C, − 1154G > A, + 936C > T and + 2578C > A VEGF polymorphisms in endometriosis patients and control were not significantly different (p > 0.05). Conclusion Our preliminary findings revealed no association between endometriosis and − 460T > C, − 1154G > A, + 936C > T and + 2578C > A of VEGF genes among Nigerian women.

scholarly journals Cytoplasmic Expression of DCLK1-S, a Novel DCLK1 Isoform, Is Associated with Tumor Aggressiveness and Worse Disease-Specific Survival in Colorectal Cancer

2021 ◽  
Author(s):  
Elham Kalantari ◽  
Roya Ghods ◽  
Leili Saeednejad Zanjani ◽  
Mandana Rahimi ◽  
Leila Eini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Polyclonal Antibody ◽  
Prognostic Significance ◽  
Rank Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Specific Survival ◽  
Cytoplasmic Expression ◽  
Advanced Tumor ◽  
Disease Specific

Abstract Background: Oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific function of DCLK1 has highlighted key role of the DCLK1-S (short isoform) in tumor maintenance, progression, and invasion. Considering the lack of commercial anti-DCLK1-S antibody suitable for immunohistochemical (IHC) application, this study was conducted to produce and validate an anti-DCLK1-S polyclonal antibody in order to specifically evaluate expression pattern and clinical significance of short isoform of DCLK1 in colorectal cancer tissues.Methods: Rabbit immunization was performed against a synthetic peptide corresponding to the published six specific amino acid sequences of DCLK1-S, and production of antibody was evaluated by enzyme-linked immunosorbent assay (ELISA). After IHC assessment of the purified anti-DCLK1-S polyclonal antibody, it was used to undertake a definitive study for determining prognostic significance of DCLK1-S expression in a well-defined tissue microarray (TMA) series including 348 CRC and 51 adjacent normal tissues with a follow-up period of 108 months. Results: Positive immunoreactivity of DCLK1-S was found in 84.2% of CRC samples. Cytoplasmic expression was the main localization of DCLK1-S compared to nuclear and membranous area of tumor cells. Expression of DCLK1-S in CRC samples was significantly higher compared to adjacent normal samples (P <0.001). A positive significant association was found between high cytoplasmic expression of DCLK1-S and advanced tumor, nodes, and metastases (TNM) stage (P<0.001) as well as the increased tumor differentiation (P= 0.02). Moreover, the patients with CRC whose tumors showed higher cytoplasmic expression of DCLK1-S had worse disease-specific survival (DSS) (log-rank test, P = 0.03) and 5-year DSS rate (P= 0.01). Additionally, the improved prognostic value was seen in the patients with CRC with high DCLK1-S expression versus moderate expression (HR: 2.70, 95% CI: 0.98-7.38; p =0.04) by multivariate analysis.Conclusions: Our findings strongly supported that DCLK1-S isoform may play a crucial role in invasion, tumor aggressive behavior, and worsened DSS of the patients with CRC. Importantly, high cytoplasmic expression of DCLK1-S compared to moderate expression could be considered as an independent prognostic factor influencing DSS. Taken together, DCLK1-S can be a candidate as a promising prognostic and targeted-therapeutic indicator for effective treatment of CRC.

scholarly journals Expression and Potential Role of MMP-9 in Intrauterine Adhesion

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Congqing Li ◽  
Wenyan Wang ◽  
Shiying Sun ◽  
Youjiang Xu ◽  
Ziang Fang ◽  
...  
Keyword(s):  
Sham Group ◽  
Endometrial Tissue ◽  
Control Group ◽  
Mrna Levels ◽  
Intrauterine Adhesions ◽  
Ctrl Group ◽  
Protein Levels ◽  
Intrauterine Adhesion ◽  
Tissue Specimens

Objective. Intrauterine adhesions affect menstruation and fertility, and endometrial fibrosis is the final manifestation of IUA. MMP-9 is closely related to fibrosis. The purpose of the study was to assess the role of MMP-9 in intrauterine adhesion (IUA) in rats and patients. Methods. 40 rats and 24 women were enrolled in this study. 40 rats were randomly divided into 3 groups: IUA group ( n = 20 ), sham group ( n = 10 ), and control group ( n = 10 ). Rat IUA models were established by intrauterine mechanical and chemical injured. In this study, 12 patients of intrauterine adhesions were detected and underwent TCRA (transcervical resection of adhesion) surgery, and endometrial tissue specimens were obtained during operation. One month later, an office hysteroscopy procedure was performed, and endometrial tissue specimens were obtained during operation again (postoperative group). A group of 12 normal age-matched control individuals served as controls underwent hysteroscopy and endometrial sampling. We used immunohistochemistry to detect MMP-9 expressions in rats and human endometrial tissues and to detect MMP-9 protein levels by Western blotting. In addition, we detected mRNA expression levels with qRT-PCR. Results. The expression of MMP-9 in the IUA rats was reduced compared with that in the sham group and Ctrl group ( P < 0.05 ), and the expression of MMP-9 was also reduced in the IUA patients compared with that in the Ctrl group ( P < 0.05 ). The mRNA levels of MMP-9 in the endometrium reflected similar results ( P < 0.05 ). The MMP-9 clearly increased even in the endometrium after TCRA surgery ( P < 0.05 ). Conclusion. Our study suggests that MMP-9 may play an important role in IUA. In the future, more in-depth research should be conducted on MMP-9.

Plantamajoside Ameliorates Inflammatory Response of Chondrocytes via Regulating NF-κB/NLRP3 Inflammasome Pathway

2021 ◽  
Vol 11 (5) ◽  
pp. 997-1002
Author(s):  
Chi Zhang ◽  
Yuanhe Wang ◽  
Chuan Hu ◽  
Kang Sun ◽  
Dingzhu Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cell Viability ◽  
Nlrp3 Inflammasome ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Apoptotic Cells ◽  
Protein Levels

The damage of articular cartilage in osteoarthritis involves the oxidative stress and inflammation. The aim of the present study was to explore the role of plantamajoside (PM) in chondrocytes and elucidate the underlying mechanism. The cell viability following treatment with PM or lipopolysac-charide (LPS) was assessed by cell counting kit-8 (CCK-8). Enzyme-Linked Immunosorbent Assay (ELISA) was supplied to determine the levels of pro-inflammatory cytokines. Moreover, the oxidative stress-related markers were evaluated via assay kits. TUNEL assay was employed to stain the apoptotic cells. The components of nuclear factor-κB (NF-κB) pathway and NLRP3 inflammasome were estimated by western blot analysis. LPS-insulted cell viability of ATDC5 was restored by PM. PM alleviated the inflammatory response and oxidative stress of ATDC5 cells induced by LPS. Furthermore, it was found that the apoptotic cells were reduced following PM treatment. The protein levels of NF-κB, IκB kinase β (IKKβ) and NLRP3 inflammasome were decreased by PM. These results suggested that PM protected the ATDC5 cells from LPS stimulation, alleviated the inflammatory response may through regulating the NF-κB and NLRP3 inflammasome.

Abstract 344: Kruppel-like Factor 15: A Critical Transcriptional Regulator of Hypoxia Induced Endothelial Arginase 2

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Deepesh Pandey ◽  
Dan Berkowitz ◽  
Lew Romer
Keyword(s):  
Endothelial Function ◽  
Chromatin Immunoprecipitation ◽  
Pulmonary Arteries ◽  
Microvascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Protein Levels ◽  
Direct Binding ◽  
Novel Therapeutic Strategies

Objective: Kruppel Like Factor 15 has recently been shown to be critical for activation of proinflammatory processes in vascular smooth muscle and atherogenesis. Although KLF15 is abundantly expressed in vascular endothelium there is a significant lack of knowledge regarding the role of KLF15 in the regulation of vascular endothelial function. Here we tested the hypothesis that a KLF15 is a critical regulator of Arg2 transcription in response to hypoxia. Approach and Results: Adenoviral mediated augmented expression of KLF15 in human pulmonary microvascular endothelial cells (HPMEC) and in rat pulmonary arteries decreased Arg2 mRNA, protein, and activity. HPMECs exposed to 48 hours of hypoxia exhibited a robust increase in Arg2 protein and mRNA expression and a reciprocal decrease in KLF15 protein levels that remain sustained after 24 hours of reoxygenation. Further, decreased KLF15 protein levels observed in hypoxia exposed HPMEC occurs through augmented conjugation of Ubiquitin to KLF15 that results in enhanced clearance of KLF15 via proteasomal degradation. Chromatin immunoprecipitation indicated direct binding of KLF15 to the Arg2 promoter, which was relieved when HPMEC were exposed to hypoxia, Finally, overexpression of KLF15 reversed hypoxia-induced augmentation of arginase activity and decrements in Nitric Oxide production in HPMEC, and also reversed hypoxia-induced endothelial dysfunction in isolated mice aortic and rat pulmonary artery rings. Conclusions: KLF15 is a critical regulator and repressor of endothelial Arg2 expression, and thereby, NO and pulmonary endothelial function. Overexpression or activation of KLF15 may represent novel therapeutic strategies for pulmonary hypertension.

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