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- Title
Upregulation of S1P1 and Rac1 receptors in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.
- Authors
Zimmer, Julia; Takahashi, Toshiaki; Duess, Johannes; Hofmann, Alejandro; Puri, Prem; Duess, Johannes W; Hofmann, Alejandro D
- Abstract
<bold>Purpose: </bold>Sphingolipids play a crucial role in pulmonary development. The sphingosine kinase 1 (SphK1) modulates the synthesis of sphingolipid sphingosine-1-phosphate (S1P). S1P regulates cell proliferation and angiogenesis via different receptors, S1P1, S1P2 and S1P3, which all influence the expression of Ras-related C3 botulinum toxin substrate 1 (Rac1). We designed this study to test the hypothesis that the S1P/Rac1 pathway is altered in the nitrofen-induced CDH model.<bold>Methods: </bold>Pregnant rats received nitrofen or vehicle on D9. On D21, fetuses were killed and divided into nitrofen and control group (n = 12). QRT-PCR, western blotting and confocal-immunofluorescence microscopy were performed to reveal pulmonary gene and protein expression levels of SphK1, S1P1, S1P2, S1P3 and Rac1.<bold>Results: </bold>Pulmonary gene expression of S1P1 and Rac1 was significantly increased in the CDH group compared to controls, whereas S1P2 and S1P3 expression was decreased. These results were confirmed by western blotting and confocal microscopy. SphK1 expression was not found to be altered.<bold>Conclusion: </bold>The increased expression of S1P1 and Rac1 in the pulmonary vasculature of nitrofen-induced CDH lungs suggests that S1P1 and Rac1 are important mediators of PH in this model.
- Subjects
DIAPHRAGMATIC hernia; SPHINGOLIPIDS; PULMONARY blood vessels; CONGENITAL disorders; NITROFEN; ANIMAL experimentation; BIOCHEMISTRY; BIOLOGICAL models; CELL receptors; GENE expression; GENES; GENETIC disorders; LUNGS; PHENOMENOLOGY; POLYMERASE chain reaction; PROTEINS; RATS; WESTERN immunoblotting; PHENYL ethers
- Publication
Pediatric Surgery International, 2016, Vol 32, Issue 2, p147
- ISSN
0179-0358
- Publication type
journal article
- DOI
10.1007/s00383-015-3825-6