Prostaglandin E 2 stimulates the production of vascular endothelial growth factor through the E-prostanoid-2 receptor in cultured human lung fibroblasts

Masanori Nakanishi, Tadashi Sato, Yingji Li, Amy J. Nelson, Maha Farid, Joel Michalski, Nobuhiro Kanaji, Xingqi Wang, Hesham Basma, Amol Patil, Jadvinder Goraya, Xiangde Liu, Shinsaku Togo, Myron L. Toews, Olaf Holz, Kai Christian Muller, Helgo Magnussen, Stephen I. Rennard

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24 Scopus citations

Abstract

Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and are a major source of vascular endothelial growth factor (VEGF), which modulates the maintenance of pulmonary microvasculature. Prostaglandin E 2 (PGE 2) actsona set of E-prostanoid (EP) receptors that activate multiple signal transduction pathways leading to downstream responses. We investigated the modulation by PGE 2 of VEGF release by human lung fibroblasts. Human lung fibroblasts were cultured until reaching 90% confluence in tissue culture plates, after which the culture media were changed to serum-free Dulbecco's modified Eagle's medium, with or without PGE 2, andwith specific agonists or antagonists for eachEP receptor. After 2 days, culturemediawereassayed for VEGF by ELISA. The results demonstrated that PGE 2 and the EP2 agonist ONO-AE1- 259-01 significantly stimulated the release of VEGF in a concentration- dependent manner. Agonists for other EP receptors did not stimulate the release of VEGF. The stimulatory effect of PGE 2 was blocked by the EP2 antagonist AH6809, but was not blocked by antagonists for other EP receptors. The protein kinase-A (PKA) inhibitor KT-5720 also blocked the stimulatory effect of PGE 2. The increased release of VEGF induced by PGE 2 was accompanied by a transient increase in the concentration of VEGF mRNA. These findings demonstrate that PGE 2 can modulate the release of VEGF by human lung fibroblasts through its actions in the EP2 receptor/ PKA pathway. This activity may contribute to the maintenance of pulmonary microvasculature in the alveolar wall.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume46
Issue number2
DOIs
StatePublished - Feb 1 2012

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Keywords

  • Human lung fibroblasts
  • Prostaglandin E
  • Tissue repair
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Nakanishi, M., Sato, T., Li, Y., Nelson, A. J., Farid, M., Michalski, J., Kanaji, N., Wang, X., Basma, H., Patil, A., Goraya, J., Liu, X., Togo, S., Toews, M. L., Holz, O., Muller, K. C., Magnussen, H., & Rennard, S. I. (2012). Prostaglandin E 2 stimulates the production of vascular endothelial growth factor through the E-prostanoid-2 receptor in cultured human lung fibroblasts. American journal of respiratory cell and molecular biology, 46(2), 217-223. https://doi.org/10.1165/rcmb.2010-0115OC