JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2014, Vol. 52 ›› Issue (10): 15-19.doi: 10.6040/j.issn.1671-7554.0.2014.351

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LPS induces lung angiogenesis via PGE2-EP2 pathway in mouse model

ZHANG Pengfei, XU Xiaoya, JIANG Man, BI Yuli, XU Jiying, HAN Mingyong   

  1. Cancer Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2014-05-30 Revised:2014-09-19 Online:2014-10-10 Published:2014-10-10

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Abstract: Objective To investigate the mechanism by which Lipopolysaccharide (LPS) induced angiogenesis in mice lungs. Methods Twelve female BALB/c mice aged 6 to 8 weeks were divided into LPS and PBS groups randomly, which were intraperitoneally injected into LPS and PBS, respectively. Lung tissues were collected to determine the pulmonary blood vessel density by HE staining and CD31 immunofluorescence staining. Vascular endothelial growth factor (VEGF) level in serum of all mice were assayed by ELISA. Mouse pulmonary vascular endothelial cells (MPVECs) were stimulated with VEGF, PGE2, Celecoxib, EP receptor inhibitor AH6809 and EP receptor agonists (ONO-AE1-259-01, ONO-DI-004, ONO-AE-248, and ONO-AE1-329). Then culture supernatant was collected to assay VEGF expression and tube forming test was performed to observe angiogenesis of endothelial cells. Results LPS induced inflammatory response and angiogenesis in mice lungs. Serum VEGF level of LPS treated mice were higher than those of PBS treated mice (P<0.01). VEGF or PGE2 used separately could increase angiogenesis. Celecoxib reduced VEGF levels released by MPVECs and suppressed angiogenesis. VEGF production was increased by ONO-AE1-259-01 (P<0.05) and decreased by AH6809 (P<0.05). Other EP receptor agonists had no significant effects on VEGF production. Conclusion LPS can induce inflammatory response in mice lungs, and increase serum VEGF level. Celecoxib can counteract this effect. LPS promotes angiogenesis by increasing the production of VEGF via PGE2-EP2 pathway.

Key words: PGE2-EP2 pathway, Angiogenesis, Lipopolysaccharide, Animal model

CLC Number: 

  • R734.2
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