Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro

Chang, Chia-Chuan; Huang, Yuan; Shyu, Ming‐Kwang; Chen, Shee‐Uan; Lin, Chin‐Feng; Ju, Tsai Kai; Lu, Jen-Her; Lee, Hsinyu

doi:10.1038/aps.2012.186

Cited by 19 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CD31 immunohistochemical staining showed an increased density of the microvessel by aFGF treatment, especially in the aFGF-HMB/UTMD group. These results correspond to a previous report on VEGF-C mRNA and VEGF-C expression through an aFGF/FGFR-1-dependent pathway in endothelial cells [43]. In our study, the expression of VEGF-C in diabetic hearts was significantly increased in the aFGF-HMB/ UTMD group, supporting the promoting effect of UTMD on aFGF penetration in DCM hearts.…”

Section: Discussionsupporting

confidence: 93%

Advanced Interfere Treatment of Diabetic Cardiomyopathy Rats by aFGF-Loaded Heparin-Modified Microbubbles and UTMD Technique

Zhang

Shen³

et al. 2016

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

This study aims to investigate the preclinical performance and mechanism of a novel strategy of aFGF-loaded heparin-modified microbubbles (aFGF-HMB) combined with ultrasound-targeted microbubble destruction (UTMD) technique for diabetic cardiomyopathy (DCM) prevention. Type 1 diabetic rats were induced by streptozotocin. Twelve weeks after intervention, indexes from transthoracic echocardiography and cardiac catheterization showed that the left ventricular function in the aFGF-HMB/UTMD group was significantly improved compared with diabetes control (DM). From Picrosirius Red staining and TUNEL staining, the aFGF-HMB/UTMD group showed significant difference from the other groups. The cardiac collagen volume fraction (CVF) and myocardial cell apoptosis index (AI) in aFGF-HMB/UTMD group decreased to 7.2 % and 7.11 % respectively, compared with the DM group (CVF = 24.5 % and AI =20.3 % respectively). The results of myocardial microvascular density (MCD) also proved the strongest inhibition of aFGF-HMB/UTMD group on DCM progress. CD31 staining of aFGF-HMB/UTMD group reached 22 n/hrp, much higher than that of DM group (9 n/hrp). These results confirmed that the abnormalities including left ventricular dysfunction, myocardial fibrosis, cardiomyocytes apoptosis and microvascular rarefaction could be suppressed by twice weekly aFGF treatments for 12 consecutive weeks (free aFGF or aFGF-HMB+/-UTMD), with the strongest improvements observed in the aFGF-HMB/UTMD group (P < 0.05 vs free aFGF or aFGF-HMB). Western blot analyses of heart tissue further revealed the highest aFGF, anti-apoptosis protein (Bcl-2), VEGF-C, pAkt, pFoxo-3a levels and strongest reduction in pro-apoptosis proteins (Bax) level in aFGF-HMB/UTMD group. Overall, aFGF-HMB combined with UTMD technique might be developed as an effective strategy to prevent DCM in future clinical therapy.

show abstract

Section: Discussionsupporting

confidence: 93%

Advanced Interfere Treatment of Diabetic Cardiomyopathy Rats by aFGF-Loaded Heparin-Modified Microbubbles and UTMD Technique

Zhang

Shen³

et al. 2016

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

show abstract

“…69e71 VEGF-C has been induced in human umbilical vein endothelial cells by sphingosine-1-phosphate, but up-regulation is blocked by inhibition of matrix metalloproteinase (MMP)-2. 72 Multiple MMPs, including MMP-2, are up-regulated in mycobacterial granuloma macrophages and thought to facilitate granuloma expansion by degrading extracellular matrix. 73e76 Together, these studies show that multiple factors that are up-regulated in granulomas can also induce VEGF-C expression.…”

Section: Discussionmentioning

confidence: 99%

Lymphangiogenesis Is Induced by Mycobacterial Granulomas via Vascular Endothelial Growth Factor Receptor-3 and Supports Systemic T-Cell Responses against Mycobacterial Antigen

Harding

Ritter

Rayasam

et al. 2015

The American Journal of Pathology

View full text Add to dashboard Cite

Granulomatous inflammation is characteristic of many autoimmune and infectious diseases. The lymphatic drainage of these inflammatory sites remains poorly understood, despite an expanding understanding of lymphatic role in inflammation and disease. Here, we show that the lymph vessel growth factor Vegf-c is up-regulated in Bacillus Calmette-Guerin- and Mycobacterium tuberculosis-induced granulomas, and that infection results in lymph vessel sprouting and increased lymphatic area in granulomatous tissue. The observed lymphangiogenesis during infection was reduced by inhibition of vascular endothelial growth factor receptor 3. By using a model of chronic granulomatous infection, we also show that lymphatic remodeling of tissue persists despite resolution of acute infection and a 10- to 100-fold reduction in the number of bacteria and tissue-infiltrating leukocytes. Inhibition of vascular endothelial growth factor receptor 3 decreased the growth of new vessels, but also reduced the proliferation of antigen-specific T cells. Together, our data show that granuloma-up-regulated factors increase granuloma access to secondary lymph organs by lymphangiogenesis, and that this process facilitates the generation of systemic T-cell responses to granuloma-contained antigens.

show abstract

“…VEGF, MMP-2 and EGFR are associated with tumor angiogenesis (52–54). In the present study, the growth of cancer cells was slowed and the migration and invasion ability reduced following COX-2 silencing.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 is associated with malignant phenotypes in human lung cancer

Yue

Wang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

The objective of the present study was to investigate whether cyclooxygenase-2 (COX-2) is associated with malignancy, and to investigate its molecular mechanisms in human lung cancer tumor malignancy. The present study used RNA interference (RNAi) methodology and celecoxib, a COX-2 inhibitor, to investigate the effect of COX-2 knockdown on the proliferation and invasion abilities of lung cancer cells and the molecular mechanisms involved. Human lung adenocarcinoma A549-si10 and LTEP-A2 cells transfected with a specific small interfering RNA (A549-si10 and LTEP-A2-si10, respectively) grew more slowly compared with parental cell lines and cells transfected with pU6. The colony formation of A549-si10 and LTEP-A2-si10 cells was also reduced. In addition, A549-si10 and LTEP-A2-si10 cells were characterized by decreased metastatic and invasive abilities. The proliferation and invasive potential of parental A549 and LTEP-A2 cells was inhibited following treatment with celecoxib. In vivo, a COX-2 knockdown resulted in a decrease of proliferation and reduction of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and endothelial growth factor receptor (EGFR) expression in A549 xenografts. In conclusion, the present study revealed that COX-2 plays a extremely important role in tumor growth, infiltration and metastasis via the regulation of VEGF, MMP-2 and EGRF expression. Therefore, COX-2 is a potential therapeutic target for lung cancer.

show abstract

Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro

Cited by 19 publications

References 32 publications

Advanced Interfere Treatment of Diabetic Cardiomyopathy Rats by aFGF-Loaded Heparin-Modified Microbubbles and UTMD Technique

Advanced Interfere Treatment of Diabetic Cardiomyopathy Rats by aFGF-Loaded Heparin-Modified Microbubbles and UTMD Technique

Lymphangiogenesis Is Induced by Mycobacterial Granulomas via Vascular Endothelial Growth Factor Receptor-3 and Supports Systemic T-Cell Responses against Mycobacterial Antigen

Cyclooxygenase-2 is associated with malignant phenotypes in human lung cancer

Contact Info

Product

Resources

About