Prostaglandin E2 switches from a stimulator to an inhibitor of cell migration after epithelial-to-mesenchymal transition

Ying Ji Li, Nobuhiro Kanaji, Xing Qi Wang, Tadashi Sato, Masanori Nakanishi, Miok Kim, Joel Michalski, Amy J. Nelson, Maha Farid, Hesham E Basma, Amol N Patil, Myron Lee Toews, Xiang-de Liu, Stephen I. Rennard

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Epithelial-mesenchymal transition (EMT) is critical for embryonic development, and this process is recapitulated in adults during wound healing, tissue regeneration, fibrosis and cancer progression. Cell migration is believed to play a key role in both normal wound repair and in abnormal tissue remodeling. Prostaglandin E2 (PGE2) inhibits fibroblast chemotaxis, but stimulates chemotaxis in airway epithelial cells. The current study was designed to explore the role of PGE2 and its four receptors on airway epithelial cell migration following EMT using both the Boyden blindwell chamber chemotaxis assay and the wound closure assay. EMT in human bronchial epithelial cells (HBECs) was induced by TGF-β1 and a mixture of cytokines (IL-1β, TNF-α, and IFN-γ). PGE2 and selective agonists for all four EP receptors stimulated chemotaxis and wound closure in HBECs. Following EMT, the EP1 and EP3 agonists were without effect, while the EP2 and EP4 agonists inhibited chemotaxis as did PGE2. The effects of the EP2 and EP4 receptors on HBEC and EMT cell migration were further confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE2 switches from a stimulator to an inhibitor of cell migration following EMT of airway epithelial cells and that this inhibition is mediated by an altered effect of EP2 and EP4 signaling and an apparent loss of the stimulatory effects of EP1 and EP3. Change in the PGE2 modulation of chemotaxis may play a role in repair following injury.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalProstaglandins and Other Lipid Mediators
Volume116-117
DOIs
StatePublished - Jan 2015

Fingerprint

Epithelial-Mesenchymal Transition
Chemotaxis
Dinoprostone
Cell Movement
Epithelial Cells
Switches
Wounds and Injuries
Assays
Repair
Tissue regeneration
Fibroblasts
Interleukin-1
Wound Healing
Embryonic Development
Regeneration
Fibrosis
Modulation
Tissue
Cytokines
Neoplasms

Keywords

  • Chemotaxis Tissue repair
  • Epithelial-mesenchymal transition
  • PGE

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

Cite this

Prostaglandin E2 switches from a stimulator to an inhibitor of cell migration after epithelial-to-mesenchymal transition. / Li, Ying Ji; Kanaji, Nobuhiro; Wang, Xing Qi; Sato, Tadashi; Nakanishi, Masanori; Kim, Miok; Michalski, Joel; Nelson, Amy J.; Farid, Maha; Basma, Hesham E; Patil, Amol N; Toews, Myron Lee; Liu, Xiang-de; Rennard, Stephen I.

In: Prostaglandins and Other Lipid Mediators, Vol. 116-117, 01.2015, p. 1-9.

Research output: Contribution to journalArticle

Li, Ying Ji ; Kanaji, Nobuhiro ; Wang, Xing Qi ; Sato, Tadashi ; Nakanishi, Masanori ; Kim, Miok ; Michalski, Joel ; Nelson, Amy J. ; Farid, Maha ; Basma, Hesham E ; Patil, Amol N ; Toews, Myron Lee ; Liu, Xiang-de ; Rennard, Stephen I. / Prostaglandin E2 switches from a stimulator to an inhibitor of cell migration after epithelial-to-mesenchymal transition. In: Prostaglandins and Other Lipid Mediators. 2015 ; Vol. 116-117. pp. 1-9.
@article{469d2fde045942daaf5813a5fd6b62d4,
title = "Prostaglandin E2 switches from a stimulator to an inhibitor of cell migration after epithelial-to-mesenchymal transition",
abstract = "Epithelial-mesenchymal transition (EMT) is critical for embryonic development, and this process is recapitulated in adults during wound healing, tissue regeneration, fibrosis and cancer progression. Cell migration is believed to play a key role in both normal wound repair and in abnormal tissue remodeling. Prostaglandin E2 (PGE2) inhibits fibroblast chemotaxis, but stimulates chemotaxis in airway epithelial cells. The current study was designed to explore the role of PGE2 and its four receptors on airway epithelial cell migration following EMT using both the Boyden blindwell chamber chemotaxis assay and the wound closure assay. EMT in human bronchial epithelial cells (HBECs) was induced by TGF-β1 and a mixture of cytokines (IL-1β, TNF-α, and IFN-γ). PGE2 and selective agonists for all four EP receptors stimulated chemotaxis and wound closure in HBECs. Following EMT, the EP1 and EP3 agonists were without effect, while the EP2 and EP4 agonists inhibited chemotaxis as did PGE2. The effects of the EP2 and EP4 receptors on HBEC and EMT cell migration were further confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE2 switches from a stimulator to an inhibitor of cell migration following EMT of airway epithelial cells and that this inhibition is mediated by an altered effect of EP2 and EP4 signaling and an apparent loss of the stimulatory effects of EP1 and EP3. Change in the PGE2 modulation of chemotaxis may play a role in repair following injury.",
keywords = "Chemotaxis Tissue repair, Epithelial-mesenchymal transition, PGE",
author = "Li, {Ying Ji} and Nobuhiro Kanaji and Wang, {Xing Qi} and Tadashi Sato and Masanori Nakanishi and Miok Kim and Joel Michalski and Nelson, {Amy J.} and Maha Farid and Basma, {Hesham E} and Patil, {Amol N} and Toews, {Myron Lee} and Xiang-de Liu and Rennard, {Stephen I.}",
year = "2015",
month = "1",
doi = "10.1016/j.prostaglandins.2014.10.003",
language = "English (US)",
volume = "116-117",
pages = "1--9",
journal = "Prostaglandins and Other Lipid Mediators",
issn = "1098-8823",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Prostaglandin E2 switches from a stimulator to an inhibitor of cell migration after epithelial-to-mesenchymal transition

AU - Li, Ying Ji

AU - Kanaji, Nobuhiro

AU - Wang, Xing Qi

AU - Sato, Tadashi

AU - Nakanishi, Masanori

AU - Kim, Miok

AU - Michalski, Joel

AU - Nelson, Amy J.

AU - Farid, Maha

AU - Basma, Hesham E

AU - Patil, Amol N

AU - Toews, Myron Lee

AU - Liu, Xiang-de

AU - Rennard, Stephen I.

PY - 2015/1

Y1 - 2015/1

N2 - Epithelial-mesenchymal transition (EMT) is critical for embryonic development, and this process is recapitulated in adults during wound healing, tissue regeneration, fibrosis and cancer progression. Cell migration is believed to play a key role in both normal wound repair and in abnormal tissue remodeling. Prostaglandin E2 (PGE2) inhibits fibroblast chemotaxis, but stimulates chemotaxis in airway epithelial cells. The current study was designed to explore the role of PGE2 and its four receptors on airway epithelial cell migration following EMT using both the Boyden blindwell chamber chemotaxis assay and the wound closure assay. EMT in human bronchial epithelial cells (HBECs) was induced by TGF-β1 and a mixture of cytokines (IL-1β, TNF-α, and IFN-γ). PGE2 and selective agonists for all four EP receptors stimulated chemotaxis and wound closure in HBECs. Following EMT, the EP1 and EP3 agonists were without effect, while the EP2 and EP4 agonists inhibited chemotaxis as did PGE2. The effects of the EP2 and EP4 receptors on HBEC and EMT cell migration were further confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE2 switches from a stimulator to an inhibitor of cell migration following EMT of airway epithelial cells and that this inhibition is mediated by an altered effect of EP2 and EP4 signaling and an apparent loss of the stimulatory effects of EP1 and EP3. Change in the PGE2 modulation of chemotaxis may play a role in repair following injury.

AB - Epithelial-mesenchymal transition (EMT) is critical for embryonic development, and this process is recapitulated in adults during wound healing, tissue regeneration, fibrosis and cancer progression. Cell migration is believed to play a key role in both normal wound repair and in abnormal tissue remodeling. Prostaglandin E2 (PGE2) inhibits fibroblast chemotaxis, but stimulates chemotaxis in airway epithelial cells. The current study was designed to explore the role of PGE2 and its four receptors on airway epithelial cell migration following EMT using both the Boyden blindwell chamber chemotaxis assay and the wound closure assay. EMT in human bronchial epithelial cells (HBECs) was induced by TGF-β1 and a mixture of cytokines (IL-1β, TNF-α, and IFN-γ). PGE2 and selective agonists for all four EP receptors stimulated chemotaxis and wound closure in HBECs. Following EMT, the EP1 and EP3 agonists were without effect, while the EP2 and EP4 agonists inhibited chemotaxis as did PGE2. The effects of the EP2 and EP4 receptors on HBEC and EMT cell migration were further confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE2 switches from a stimulator to an inhibitor of cell migration following EMT of airway epithelial cells and that this inhibition is mediated by an altered effect of EP2 and EP4 signaling and an apparent loss of the stimulatory effects of EP1 and EP3. Change in the PGE2 modulation of chemotaxis may play a role in repair following injury.

KW - Chemotaxis Tissue repair

KW - Epithelial-mesenchymal transition

KW - PGE

UR - http://www.scopus.com/inward/record.url?scp=84911933373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84911933373&partnerID=8YFLogxK

U2 - 10.1016/j.prostaglandins.2014.10.003

DO - 10.1016/j.prostaglandins.2014.10.003

M3 - Article

C2 - 25460827

AN - SCOPUS:84911933373

VL - 116-117

SP - 1

EP - 9

JO - Prostaglandins and Other Lipid Mediators

JF - Prostaglandins and Other Lipid Mediators

SN - 1098-8823

ER -