Hypoxia Regulates Expression of the Endothelin-1 Gene through a Proximal Hypoxia-Inducible Factor-1 Binding Site on the Antisense Strand

Hu, Jing; Discher, Daryl J.; Bishopric, Nanette H.; Webster, Keith A.

doi:10.1006/bbrc.1998.8543

Cited by 240 publications

(141 citation statements)

References 51 publications

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“…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

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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.

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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

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“…We examined the activity of the full-length ET-1 promoter (669 bp) (19,38), which has three KLF-11 cis-binding sites and a single HRE site, with a luciferase reporter gene as depicted in Fig. 6G.…”

Section: Does Plgf-mediated Induction Of Et-1 Expression Involve Krupmentioning

confidence: 99%

Peroxisome Proliferator-activated Receptor-α-mediated Transcription of miR-199a2 Attenuates Endothelin-1 Expression via Hypoxia-inducible Factor-1α

Li¹,

Mpollo

Gonsalves³

et al. 2014

Journal of Biological Chemistry

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Background: Elevated plasma levels of PlGF are associated with increased endothelin-1 and pulmonary hypertension (PH) in SCD. Results: miR-199a2, which targets HIF-1␣ mRNA, located in host gene DNM3os is co-transcriptionally regulated by PPAR␣. Conclusion: PPAR␣ agonist induction of miR-199a2 reduced ET-1 levels. Significance: PPAR␣ agonist reduction of ET-1 levels via induced miR-199a2 provides an alternative strategy to ameliorate PH.

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“…They are also mitogens for endothelial cells, fibroblasts and vascular smooth muscle cells. [20][21][22] Endothelins trigger the production of angiogenic factors in response to hypoxia and may have a role in tumor neovascularization. [23][24][25] Since the endothelin is produced and activates mitogenic signaling in several human cancer cells, and interact with VEGF, its promoter can be used to direct genes specifically into the vascular bed in this process.…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific gene therapy directed to tumor angiogenesis

et al. 2001

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Gene therapy directed specifically to the vascular wall, particularly to angiogenic endothelial cells is a prerequisite in vascular disease treatment. Angiogenesis is a major feature in many pathological conditions including wound healing, solid tumors, developing metastases, ischemic heart diseases and diabetic retinopathy. In the present study we developed a tissue-specific gene therapy to the angiogenic blood vessels of tumor metastasis using an adeno-based vector containing the murine preproendothelin-1 (PPE-1) promoter. Genes activated by the PPE-1 promoter were highly expressed in bovine aortic endothelial cells in vitro. Systemic injection of the adenoviral vectors AdPPE-1-

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Hypoxia Regulates Expression of the Endothelin-1 Gene through a Proximal Hypoxia-Inducible Factor-1 Binding Site on the Antisense Strand

Cited by 240 publications

References 51 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

Peroxisome Proliferator-activated Receptor-α-mediated Transcription of miR-199a2 Attenuates Endothelin-1 Expression via Hypoxia-inducible Factor-1α

Tissue-specific gene therapy directed to tumor angiogenesis

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