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 language | English (US) |
|---|---|
| Pages (from-to) | 99-107 |
| Number of pages | 9 |
| Journal | American journal of respiratory cell and molecular biology |
| Volume | 44 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2010 |
Fingerprint
Keywords
- Cell migration
- EP receptors
- Human lung fibroblast
ASJC Scopus subject areas
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology
Cite this
Prostaglandin E2 inhibits human lung fibroblast chemotaxis through disparate actions on different E-prostanoid receptors. / Li, Ying Ji; Wang, Xing Qi; Sato, Tadashi; Kanaji, Nobuhiro; Nakanishi, Masanori; Kim, Miok; Michalski, Joel; Nelson, Amy J.; Sun, Jian Hong; Farid, Maha; Basma, Hesham E; Patil, Amol N; Toews, Myron Lee; Liu, Xiang-de; Rennard, Stephen I.
In: American journal of respiratory cell and molecular biology, Vol. 44, No. 1, 01.01.2010, p. 99-107.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prostaglandin E2 inhibits human lung fibroblast chemotaxis through disparate actions on different E-prostanoid receptors
AU - Li, Ying Ji
AU - Wang, Xing Qi
AU - Sato, Tadashi
AU - Kanaji, Nobuhiro
AU - Nakanishi, Masanori
AU - Kim, Miok
AU - Michalski, Joel
AU - Nelson, Amy J.
AU - Sun, Jian Hong
AU - Farid, Maha
AU - Basma, Hesham E
AU - Patil, Amol N
AU - Toews, Myron Lee
AU - Liu, Xiang-de
AU - Rennard, Stephen I.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Cell migration
KW - EP receptors
KW - Human lung fibroblast
UR - http://www.scopus.com/inward/record.url?scp=78650640662&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650640662&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2009-0163OC
DO - 10.1165/rcmb.2009-0163OC
M3 - Article
C2 - 20203295
AN - SCOPUS:78650640662
VL - 44
SP - 99
EP - 107
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 1
ER -