Phospholipase Cγ activation drives increased production of autotaxin in endothelial cells and lysophosphatidic acid-dependent regression

Eunok Im, Ruta Motiejunaite, Jorge Aranda, Eun Young Park, Lorenzo Federico, Tae Im Kim, Timothy Clair, Mary L. Stracke, Susan Smyth, Andrius Kazlauskas

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32 Citations (Scopus)

Abstract

We previously reported that vascular endothelial growth factor (VEGF)-dependent activation of phospholipase Cγ1 (PLCγ) regulated tube stability by competing with phosphoinositide 3-kinase (PI3K) for their common substrate. Here we describe an additional mechanism by which PLCγ promoted regression of tubes and blood vessels. Namely, it increased the level of autotaxin (ATX), which is a secreted form of lysophospholipase D that produces lysophosphatidic acid (LPA). LPA promoted motility of endothelial cells, leading to disorganization/regression of tubes in vitro. Furthermore, mice that under- or overexpressed members of this intrinsic destabilization pathway showed either delayed or accelerated, respectively, regression of blood vessels. We conclude that endothelial cells can be instructed to engage a PLCγ-dependent intrinsic destabilization pathway that results in the production of soluble regression factors such as ATX and LPA. These findings are likely to potentiate ongoing efforts to prevent, manage, and eradicate numerous angiogenesis-based diseases such as proliferative diabetic retinopathy and solid tumors.

Original languageEnglish
Pages (from-to)2401-2410
Number of pages10
JournalMolecular and cellular biology
Volume30
Issue number10
DOIs
Publication statusPublished - 2010 May

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Im, E., Motiejunaite, R., Aranda, J., Park, E. Y., Federico, L., Kim, T. I., Clair, T., Stracke, M. L., Smyth, S., & Kazlauskas, A. (2010). Phospholipase Cγ activation drives increased production of autotaxin in endothelial cells and lysophosphatidic acid-dependent regression. Molecular and cellular biology, 30(10), 2401-2410. https://doi.org/10.1128/MCB.01275-09