Sprouty1 inhibits angiogenesis in association with up-regulation of p21 and p27

Sangjin Lee, Tri M.Bui Nguyen, Dmitry Kovalenko, Neeta Adhikari, Suzanne Grindle, Sean P. Polster, Robert Friesel, Sundaram Ramakrishnan, Jennifer L. Hall

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Sprouty1 (Spry1) is a conserved antagonist of FGF signaling. The goal of this study was to further explore the downstream mechanisms governing Spry1 inhibition of endothelial cell proliferation. Up-regulation of Spry1 in HUVECs inhibited tube formation on Matrigel (n = 6, P < 0.001). This was associated with decreased proliferation as measured by BrdU incorporation (n = 6, P < 0.001) and increased protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A), p21 and cyclin-dependent kinase inhibitor 1B (CDKN1B), p27. A transcriptional analysis using a targeted human angiogenesis array following up-regulation of Spry1 demonstrated a >2-fold increase in an anti-angiogenic factor, serpin peptidase inhibitor, clad F (Serpinf1), and a >2-fold decrease in pro-angiogenic factors fms-related tyrosine kinase 1 (FLT1), angiopoietin2 (Ang-2), and placental growth factor (PGF) (n = 2). To define upstream mechanisms that may regulate endogenous Spry1, we performed a search for responsive elements upstream of the promoter region. This search resulted in the identification of multiple degenerate hypoxia responsive elements. Exposure to hypoxia resulted in a significant increase in Spry1 expression (n = 8, P < 0.01). These findings shed new light on downstream signaling pathways associated with Spry1 anti-proliferative responses, and provide new evidence that hypoxia stimulates Spry1 expression.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalMolecular and Cellular Biochemistry
Volume338
Issue number1-2
DOIs
StatePublished - May 1 2010
Externally publishedYes

Fingerprint

Angiogenesis Inducing Agents
Up-Regulation
Serpins
Endothelial cells
Cell proliferation
Protease Inhibitors
Genetic Promoter Regions
Protein-Tyrosine Kinases
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Cell Proliferation
Hypoxia
matrigel

Keywords

  • Endothelial cell
  • HIF
  • HUVEC
  • Hypoxia
  • Serpinf1

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Lee, S., Nguyen, T. M. B., Kovalenko, D., Adhikari, N., Grindle, S., Polster, S. P., ... Hall, J. L. (2010). Sprouty1 inhibits angiogenesis in association with up-regulation of p21 and p27. Molecular and Cellular Biochemistry, 338(1-2), 255-261. https://doi.org/10.1007/s11010-009-0359-z

Sprouty1 inhibits angiogenesis in association with up-regulation of p21 and p27. / Lee, Sangjin; Nguyen, Tri M.Bui; Kovalenko, Dmitry; Adhikari, Neeta; Grindle, Suzanne; Polster, Sean P.; Friesel, Robert; Ramakrishnan, Sundaram; Hall, Jennifer L.

In: Molecular and Cellular Biochemistry, Vol. 338, No. 1-2, 01.05.2010, p. 255-261.

Research output: Contribution to journalArticle

Lee, S, Nguyen, TMB, Kovalenko, D, Adhikari, N, Grindle, S, Polster, SP, Friesel, R, Ramakrishnan, S & Hall, JL 2010, 'Sprouty1 inhibits angiogenesis in association with up-regulation of p21 and p27', Molecular and Cellular Biochemistry, vol. 338, no. 1-2, pp. 255-261. https://doi.org/10.1007/s11010-009-0359-z
Lee S, Nguyen TMB, Kovalenko D, Adhikari N, Grindle S, Polster SP et al. Sprouty1 inhibits angiogenesis in association with up-regulation of p21 and p27. Molecular and Cellular Biochemistry. 2010 May 1;338(1-2):255-261. https://doi.org/10.1007/s11010-009-0359-z
Lee, Sangjin ; Nguyen, Tri M.Bui ; Kovalenko, Dmitry ; Adhikari, Neeta ; Grindle, Suzanne ; Polster, Sean P. ; Friesel, Robert ; Ramakrishnan, Sundaram ; Hall, Jennifer L. / Sprouty1 inhibits angiogenesis in association with up-regulation of p21 and p27. In: Molecular and Cellular Biochemistry. 2010 ; Vol. 338, No. 1-2. pp. 255-261.
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