Prostaglandin E2 inhibits human lung fibroblast chemotaxis through disparate actions on different E-prostanoid receptors

Ying Ji Li, Xing Qi Wang, Tadashi Sato, Nobuhiro Kanaji, Masanori Nakanishi, Miok Kim, Joel Michalski, Amy J. Nelson, Jian Hong Sun, Maha Farid, Hesham Basma, Amol Patil, Myron L. Toews, Xiangde Liu, Stephen I. Rennard

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The migration of fibroblasts is believed to play a key role in both normal wound repair and abnormal tissue remodeling. Prostaglandin E (PGE)2, a mediator that can inhibit many fibroblast functions including chemotaxis, was reported to be mediated by the E-prostanoid (EP) receptor EP2. PGE2, however, can act on four receptors. This study was designed to determine if EP receptors, in addition to EP2, can modulate fibroblast chemotaxis. Using human fetal lung fibroblasts, the expression of all four EP receptors was demonstrated by Western blotting. EP2-selective and EP4-selective agonists inhibited both chemotaxis toward fibronectin in the blindwell assay and migration in a wound-closure assay. In contrast, EP1-selective and EP3-selective agonists stimulated cell migration in both assay systems. These results were confirmed using EP-selective antagonists. The role of both EP2 and EP4 receptors in mediating the PGE2 inhibition of chemotaxis was also confirmed by small interfering RNA suppression. Furthermore, the role of EP receptors was confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE2 can act on multiple EP receptors in human lung fibroblasts, to exert disparate effects. Alterations in EP receptor expression may have the potential to alter PGE2 action. Targeting specific EP receptors may offer therapeutic opportunities in conditions characterized by abnormal tissue repair and remodeling.

Original languageEnglish (US)
Pages (from-to)99-107
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume44
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Cell migration
  • EP receptors
  • Human lung fibroblast

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Prostaglandin E<sub>2</sub> inhibits human lung fibroblast chemotaxis through disparate actions on different E-prostanoid receptors'. Together they form a unique fingerprint.

  • Cite this