Hypoxia and endothelin-1 induce VEGF production in human vascular smooth muscle cells

Okuda, Yukichi; Tsurumaru, Kazuki; Suzuki, Seiji; Miyauchi, Takashi; Asano, Michiko; Hong, Ying; Sone, Hirohito; Fujita, Rie; Mizutani, Masakazu; Kawakami, Yasushi; Nakajima, Toshiaki; Soma, Masaaki; Matsuo, Katsuhiko; Suzuki, Hideo; Yamashita, Kamejiro

doi:10.1016/s0024-3205(98)00296-3

Cited by 58 publications

(47 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance endothelin 1 is a hypoxia inducible HIF-1 target gene (Hieda and GomezSanchez, 1990;Hu et al, 1998) capable of stimulating proliferation and migration, inducing VEGF production (Okuda et al, 1998;Kozawa et al, 2000), and increasing the expression of various proto-oncogenes (Yin et al, 1992;Herman and Simonson, 1995). Interestingly, several of the VHL regulated genes have potential roles in matrix metabolism.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

et al. 2000

View full text Add to dashboard Cite

The von Hippel-Lindau tumour suppressor gene (VHL) targets hypoxia inducible factor (HIF)-a subunits for ubiquitin dependent proteolysis. To better understand the role of this and other putative pathways of gene regulation in VHL function we subjected mRNA from VHL defective renal carcinoma cells and transfectants re-expressing a wild type VHL allele to di erential expression pro®ling, and analysed VHL target genes for oxygen regulated expression. Among a group of newly identi®ed VHL target genes the majority but not all were regulated by oxygen, indicating that whilst dysregulation of the HIF system makes a dominant contribution to alterations in transcription, VHL has other in¯uences on patterns of gene expression. Genes newly de®ned as targets of the VHL/hypoxia pathway (conditionally downregulated by VHL in normoxic cells) include aminopeptidase A, collagen type V, alpha 1, cyclin G2, DEC1/Stra13, endothelin 1, low density lipoprotein receptor-related protein 1, MIC2/CD99, and transglutaminase 2. These genes have a variety of functions relevant to tumour biology. However, not all are connected with the promotion of tumour growth, some being pro-apoptotic or growth inhibitory. We postulate that co-ordinate regulation as part of the HIF pathway may explain this paradox, and that evolution of antiapoptotic pathways may be required for tumour growth under VHL-dysregulation. Our results indicate that it will be necessary to consider the e ects of abnormal activity in integral regulatory pathways, as well as the e ects of individual genes to understand the role of abnormal patterns of gene expression in cancer. Oncogene (2000) 19, 6297 ± 6305.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

et al. 2000

View full text Add to dashboard Cite

show abstract

“…In addition to such direct effects, ET-1 may indirectly increase vascular endothelial growth factor and induce hypoxia-inducing factor 1-a (90). ET-1 and vascular endothelial growth factor stimulate one another (91), resulting in the proliferation of endothelial and vascular smooth muscle cells thus promoting tumor growth. Previous work also shows a role for tumor-secreted ET-1 in skeletal metastases from breast and prostate cancers (92) and supports a model in which tumor-secreted ET-1 stimulates bone cells, in turn, providing a fertile microenvironment for metastases.…”

Section: Clinical-translational Advancesmentioning

confidence: 99%

Metastasis Suppressor Proteins: Discovery, Molecular Mechanisms, and Clinical Application

Rinker‐Schaeffer

O’Keefe

Welch

et al. 2006

Clinical Cancer Research

119

View full text Add to dashboard Cite

Clinically and experimentally, primary tumor formation and metastasis are distinct processes -locally growing tumors can progress without the development of metastases. This observation prompted the hypothesis that the molecular processes regulating tumorigenicity and metastasis are distinguishable and could be targeted therapeutically. During the process of transformation and subsequent progression to a malignant phenotype, both genetic and epigenetic alterations alter a cell's ability to perceive and respond to signals that regulate normal tissue homeostasis. A minority of tumorigenic cells accrue the full complement of alterations that enables them to disseminate from the primary tumor, survive insults from the immune system and biophysical forces, and respond to growthpromoting and/or inhibitory signals from the distant tissues and thrive there. Identification of genes and proteins that specifically inhibit the ability of cells to form metastases (e.g., metastasis suppressors) is providing new insights into the molecular mechanisms that regulate this complex process. This review will highlight: (a) the functional identification of metastasis suppressors, (b) the signaling cascades and cellular phenotypes which are controlled or modulated by metastasis suppressors, and (c) opportunities for translation and clinical trials that are based on mechanistic studies regarding metastasis suppressors.

show abstract

“…First of all, the estimation of protein concentrations in the serum has a low specificity, especially in chronic and advanced cardiovascular diseases, where chronic hypoxia of the organs and tissues may have a significant influence on the total VEGF concentration in the blood. It is well known that hypoxia is one of the strongest factors that upregulates VEGF-A expression [14,[19][20][21][22][23]. In the acute phase of the disease, the expression of genes and receptors may change profoundly with different strengths and at different times.…”

Section: Discussionmentioning

confidence: 99%

“…It must also be remembered that the proangiogenic activity of VEGF-A may be influenced by the amount and type of isoforms, which are determined by alternative splicing of mRNA [1,2,4]. The mechanisms of that process are still unknown, but most probably the presence of particular VEGF-A isoforms is determined and regulated by metabolic processes and the microenvironment [1,20,[24][25][26][27]. This hypothesis is supported by the results of the presented study, where a significant increase in VEGF-A mRNA expression was observed in hearts with post-inflammatory etiology of cardiomyopathy compared to idiopathic.…”

Section: Discussionmentioning

confidence: 99%

“…This was probably related to the inflammation which had occured in these similar hearts and with inflammatory mediators released during this process. Many studies proved that different mediators and growth factors regulate VEGF synthesis and even take part in different levels of the angiogenic cascade via VEGF and its receptors [1,12,20,24,25,27,[41][42][43]. The higher transcriptional activity of VEGF-A and the associated high concentrations of VEGF-A isoforms in myocarditis result in bigger cardiomyocytes oedema, because VEGF is a known vascular permeability factor [1][2][3][4][5]26].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Post-transcriptional modifications of VEGF-A mRNA in non-ischemic dilated cardiomyopathy

Kowalczyk

Domal-Kwiatkowska

Mazurek

et al. 2007

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF-A) is one of the most important proangiogenic factors. It has many isoforms encoded by one gene. The occurrence of these isoforms is associated with the process of alternative splicing of mRNA. Some of the splice forms are perceived as tissue specific. The aim of this study was to determine the alternative splicing of VEGF-A mRNA in dilated cardiomyopathy, especially at the level of particular myocardial layers. The assessment of post-transcriptional modifications of VEGF-A mRNA was made on specimens taken from the explanted hearts of patients undergoing cardiac transplantation. Molecular and histopathological studies were perfomed on particular layers of the myocardial muscle (endocardium, myocardium, epicardium). A molecular analysis of cardiac samples was performed by quantitative analysis of the mRNA of the studied VEGF-A isoforms (VEGF121, -145, -165, -183, -189, and -206) using QRTPCR with an ABI-PRISM 7700-TaqMan sequence detector. 72 cardiac specimens taken from the explanted hearts were analyzed. Each of the studied VEGF-A splice forms was present in the evaluated hearts, but the types of alternative splicing of mRNA were different in particular layers. Quantitative analysis revealed different amounts of the studied isoforms. Generally, significantly increased expression of the VEGF-A isoforms was observed in samples taken from hearts with post-inflammatory etiology of cardiomyopathy. Our conclusions are: 1. All the studied VEGF-A isoforms were found in the human hearts, including those thusfar considered characteristic for other tissues. 2. Significant differences were observed in the expression of the VEGF-A splice forms with respect to the myocardial layers and the location of the cardiac biopsy. 3. Repetitive and comparable results for samples with post-inflammatory etiology were obtained, and they revealed considerably higher amounts of VEGF-A isoforms compared to specimens with idiopathic etiology.

show abstract

Hypoxia and endothelin-1 induce VEGF production in human vascular smooth muscle cells

Cited by 58 publications

References 14 publications

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

Metastasis Suppressor Proteins: Discovery, Molecular Mechanisms, and Clinical Application

Post-transcriptional modifications of VEGF-A mRNA in non-ischemic dilated cardiomyopathy

Contact Info

Product

Resources

About