{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:25:41Z","timestamp":1791257141708,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 E2 (PGE2) acts on a set of E-prostanoid (EP) receptors that activate multiple signal transduction pathways leading to downstream responses. We investigated the modulation by PGE2 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 PGE2, and with specific agonists or antagonists for each EP receptor. After 2 days, culture media were assayed for VEGF by ELISA. The results demonstrated that PGE2 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 PGE2 was blocked by the EP2 antagonist AH6809, but was not blocked by antagonists for other EP receptors. The protein kinase\u2013A (PKA) inhibitor KT-5720 also blocked the stimulatory effect of PGE2. The increased release of VEGF induced by PGE2 was accompanied by a transient increase in the concentration of VEGF mRNA. These findings demonstrate that PGE2 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.<\/jats:p>","DOI":"10.1165\/rcmb.2010-0115oc","type":"journal-article","created":{"date-parts":[[2011,9,16]],"date-time":"2011-09-16T07:01:24Z","timestamp":1316156484000},"page":"217-223","source":"Crossref","is-referenced-by-count":25,"title":["Prostaglandin E2 Stimulates the Production of Vascular Endothelial Growth Factor through the E-Prostanoid\u20132 Receptor in Cultured Human Lung Fibroblasts"],"prefix":"10.1093","volume":"46","author":[{"given":"Masanori","family":"Nakanishi","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingji","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Farid","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Michalski","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Kanaji","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham","family":"Basma","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol","family":"Patil","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadvinder","family":"Goraya","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangde","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsaku","family":"Togo","sequence":"additional","affiliation":[{"name":"School of Medicine, Juntendo University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myron","family":"L. 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