Bernacchioni C, Capezzuoli T, Vannuzzi V, et al. - Researchers conducted a case-control laboratory study in order to determine the molecular mechanisms involved in the appearance of the fibrotic trait in endometriosis by examining whether the signaling pathway of the bioactive sphingolipid sphingosine 1-phosphate (S1P) was altered in endometriotic lesions. They analyzed endometrial samples obtained from women affected (n = 15 endometrioma [OMA]; n = 30 deep infiltrating endometriosis [DIE]) and not (n = 30) by endometriosis by means of laparoscopic surgery. In mRNA expression analysis of S1PR, a deep dysregulation of S1P signaling in endometriosis was noted, which is characterized by raised expression of fibrosis markers: S1P 1 was transcriptionally more expressed in OMA, and S1P 3 and S1P 5 mRNA levels were significantly augmented in both OMA and DIE. OMA and DIE showed significant up-regulation of SK1 and its activating protein calcium- and integrin-binding protein 1 (CIB1). In vitro findings highlight a crucial role for the SK/S1PR axis in the profibrotic effect elicited by TGFβ1. This study overall suggests the possible value of S1P signaling axis as a valuable biomarker or innovative pharmacologic target for endometriosis.