Skip to main content
Journal cover image

ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression.

Publication ,  Journal Article
Lux, A; Salway, F; Dressman, HK; Kröner-Lux, G; Hafner, M; Day, PJR; Marchuk, DA; Garland, J
Published in: BMC Cardiovasc Disord
April 4, 2006

BACKGROUND: TGF-beta1 is an important angiogenic factor involved in the different aspects of angiogenesis and vessel maintenance. TGF-beta signalling is mediated by the TbetaRII/ALK5 receptor complex activating the Smad2/Smad3 pathway. In endothelial cells TGF-beta utilizes a second type I receptor, ALK1, activating the Smad1/Smad5 pathway. Consequently, a perturbance of ALK1, ALK5 or TbetaRII activity leads to vascular defects. Mutations in ALK1 cause the vascular disorder hereditary hemorrhagic telangiectasia (HHT). METHODS: The identification of ALK1 and not ALK5 regulated genes in endothelial cells, might help to better understand the development of HHT. Therefore, the human microvascular endothelial cell line HMEC-1 was infected with a recombinant constitutively active ALK1 adenovirus, and gene expression was studied by using gene arrays and quantitative real-time PCR analysis. RESULTS: After 24 hours, 34 genes were identified to be up-regulated by ALK1 signalling. Analysing ALK1 regulated gene expression after 4 hours revealed 13 genes to be up- and 2 to be down-regulated. Several of these genes, including IL-8, ET-1, ID1, HPTPeta and TEAD4 are reported to be involved in angiogenesis. Evaluation of ALK1 regulated gene expression in different human endothelial cell types was not in complete agreement. Further on, disparity between constitutively active ALK1 and TGF-beta1 induced gene expression in HMEC-1 cells and primary HUVECs was observed. CONCLUSION: Gene array analysis identified 49 genes to be regulated by ALK1 signalling and at least 14 genes are reported to be involved in angiogenesis. There was substantial agreement between the gene array and quantitative real-time PCR data. The angiogenesis related genes might be potential HHT modifier genes. In addition, the results suggest endothelial cell type specific ALK1 and TGF-beta signalling.

Duke Scholars

Published In

BMC Cardiovasc Disord

DOI

EISSN

1471-2261

Publication Date

April 4, 2006

Volume

6

Start / End Page

13

Location

England

Related Subject Headings

  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Transcription Factors
  • Receptors, Cytoplasmic and Nuclear
  • Neovascularization, Physiologic
  • Humans
  • Gene Expression Regulation
  • Endothelium, Vascular
  • Endothelial Cells
  • Constitutive Androstane Receptor
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lux, A., Salway, F., Dressman, H. K., Kröner-Lux, G., Hafner, M., Day, P. J. R., … Garland, J. (2006). ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression. BMC Cardiovasc Disord, 6, 13. https://doi.org/10.1186/1471-2261-6-13
Lux, Andreas, Fiona Salway, Holly K. Dressman, Gabriele Kröner-Lux, Mathias Hafner, Philip J. R. Day, Douglas A. Marchuk, and John Garland. “ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression.BMC Cardiovasc Disord 6 (April 4, 2006): 13. https://doi.org/10.1186/1471-2261-6-13.
Lux A, Salway F, Dressman HK, Kröner-Lux G, Hafner M, Day PJR, et al. ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression. BMC Cardiovasc Disord. 2006 Apr 4;6:13.
Lux, Andreas, et al. “ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression.BMC Cardiovasc Disord, vol. 6, Apr. 2006, p. 13. Pubmed, doi:10.1186/1471-2261-6-13.
Lux A, Salway F, Dressman HK, Kröner-Lux G, Hafner M, Day PJR, Marchuk DA, Garland J. ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression. BMC Cardiovasc Disord. 2006 Apr 4;6:13.
Journal cover image

Published In

BMC Cardiovasc Disord

DOI

EISSN

1471-2261

Publication Date

April 4, 2006

Volume

6

Start / End Page

13

Location

England

Related Subject Headings

  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Transcription Factors
  • Receptors, Cytoplasmic and Nuclear
  • Neovascularization, Physiologic
  • Humans
  • Gene Expression Regulation
  • Endothelium, Vascular
  • Endothelial Cells
  • Constitutive Androstane Receptor