Astrocytic thrombin-evoked VEGF release is dependent on p44/42 MAPKs and PAR1

Biochem Biophys Res Commun. 2019 Feb 5;509(2):585-589. doi: 10.1016/j.bbrc.2018.12.168. Epub 2018 Dec 31.

Abstract

Intracerebral haemorrhage (ICH) often causes severe neurological deficits in survived patients, although its underlying mechanisms remain elusive. A common feature of ICH is the accumulation of thrombin around the lesion site. Previous studies showed that thrombin promotes VEGF release and angiogenesis at a late stage post ICH [1]. In current study, we explored the source for thrombin-induced VEGF release by adding thrombin or its receptor agonist peptide to the neuronal or astrocytic primarily cultures. We identified that astrocytes specifically respond to thrombin by up-regulating and releasing VEGF. Furthermore, such release is dependent on p44/42 MAPKs and PAR1, a thrombin specific receptor. Our study therefore helps clarifying the underlying mechanisms of thrombin-induced VEGF release in ICH, which will further provide novel insights into the designing principles for treating ICH and traumatic brain injuries.

Keywords: Astrocyte; ICH; MAPKs; PAR-1; Thrombin; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Cells, Cultured
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Rats, Sprague-Dawley
  • Receptor, PAR-1 / genetics
  • Receptor, PAR-1 / metabolism*
  • Thrombin / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Receptor, PAR-1
  • Vascular Endothelial Growth Factor A
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Thrombin