Sphingosine 1-phosphate signaling in uterine fibroids: implication in activin A pro-fibrotic effect

ObjectiveTo explore the link between sphingosine 1-phosphate (S1P) signaling and leiomyoma possible S1P cross-talk with fibrotic effect of activin A.DesignCase-control laboratory study.SettingUniversity institute university hospital.Patient(s)Patients uterine fibroids (n = 26).Interventions(s)Tissue specimens normal myometrium were obtained from patients undergoing myomectomy or total hysterectomy.Main Outcome Measure(s)Expression mRNA levels enzyme involved in metabolism, receptors, transporter Spns2 was evaluated matched leiomyoma/myometrium cell populations. The effects inhibition metabolism on A–induced action lines.Result(s)The expression enzymes responsible for formation, kinase (SK) 1 2, S1P2, S1P3, S1P5 receptors significantly augmented leiomyomas compared adjacent myometrium. In cells, but not myometrial A increased SK1, SK2, S1P2. profibrotic abolished when SK1/2 inhibited S1P2/3 blocked. Finally, by itself markers (fibronectin, collagen 1A1) cells.Conclusion(s)This study shows that is dysregulated fibrosis, opening new perspectives fibroid treatment. To A. Case-control study. University hospital. Patients 26). Tissue hysterectomy. Expression lines. cells. This