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Endoglin mediates fibronectin/α5β1 integrin and TGF-β pathway crosstalk in endothelial cells.

Publication ,  Journal Article
Tian, H; Mythreye, K; Golzio, C; Katsanis, N; Blobe, GC
Published in: EMBO J
October 3, 2012

Both the transforming growth factor β (TGF-β) and integrin signalling pathways have well-established roles in angiogenesis. However, how these pathways integrate to regulate angiogenesis is unknown. Here, we show that the extracellular matrix component, fibronectin, and its cellular receptor, α5β1 integrin, specifically increase TGF-β1- and BMP-9-induced Smad1/5/8 phosphorylation via the TGF-β superfamily receptors endoglin and activin-like kinase-1 (ALK1). Fibronectin and α5β1 integrin increase Smad1/5/8 signalling by promoting endoglin/ALK1 cell surface complex formation. In a reciprocal manner, TGF-β1 activates α5β1 integrin and downstream signalling to focal adhesion kinase (FAK) in an endoglin-dependent manner. α5β1 integrin and endoglin form a complex on the cell surface and co-internalize, with their internalization regulating α5β1 integrin activation and signalling. Functionally, endoglin-mediated fibronectin/α5β1 integrin and TGF-β pathway crosstalk alter the responses of endothelial cells to TGF-β1, switching TGF-β1 from a promoter to a suppressor of migration, inhibiting TGF-β1-mediated apoptosis to promote capillary stability, and partially mediating developmental angiogenesis in vivo. These studies provide a novel mechanism for the regulation of TGF-β superfamily signalling and endothelial function through crosstalk with integrin signalling pathways.

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Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

October 3, 2012

Volume

31

Issue

19

Start / End Page

3885 / 3900

Location

England

Related Subject Headings

  • Transforming Growth Factor beta1
  • Smad8 Protein
  • Smad5 Protein
  • Smad1 Protein
  • Signal Transduction
  • Receptors, Cell Surface
  • Phosphorylation
  • Neovascularization, Physiologic
  • Microvessels
  • Integrin alpha5beta1
 

Citation

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Tian, H., Mythreye, K., Golzio, C., Katsanis, N., & Blobe, G. C. (2012). Endoglin mediates fibronectin/α5β1 integrin and TGF-β pathway crosstalk in endothelial cells. EMBO J, 31(19), 3885–3900. https://doi.org/10.1038/emboj.2012.246
Tian, Hongyu, Karthikeyan Mythreye, Christelle Golzio, Nicholas Katsanis, and Gerard C. Blobe. “Endoglin mediates fibronectin/α5β1 integrin and TGF-β pathway crosstalk in endothelial cells.EMBO J 31, no. 19 (October 3, 2012): 3885–3900. https://doi.org/10.1038/emboj.2012.246.
Tian H, Mythreye K, Golzio C, Katsanis N, Blobe GC. Endoglin mediates fibronectin/α5β1 integrin and TGF-β pathway crosstalk in endothelial cells. EMBO J. 2012 Oct 3;31(19):3885–900.
Tian, Hongyu, et al. “Endoglin mediates fibronectin/α5β1 integrin and TGF-β pathway crosstalk in endothelial cells.EMBO J, vol. 31, no. 19, Oct. 2012, pp. 3885–900. Pubmed, doi:10.1038/emboj.2012.246.
Tian H, Mythreye K, Golzio C, Katsanis N, Blobe GC. Endoglin mediates fibronectin/α5β1 integrin and TGF-β pathway crosstalk in endothelial cells. EMBO J. 2012 Oct 3;31(19):3885–3900.

Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

October 3, 2012

Volume

31

Issue

19

Start / End Page

3885 / 3900

Location

England

Related Subject Headings

  • Transforming Growth Factor beta1
  • Smad8 Protein
  • Smad5 Protein
  • Smad1 Protein
  • Signal Transduction
  • Receptors, Cell Surface
  • Phosphorylation
  • Neovascularization, Physiologic
  • Microvessels
  • Integrin alpha5beta1