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Updated: Feb 10, 2026
A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A
Jung H Suh1, Émilie Degagné1, Elizabeth E Gleghorn1
1UCSF Benioff Children's Hospital Oakland, Oakland, Califorina, USA.
Insights
Pediatric inflammatory bowel disease (IBD) patients show increased sphingosine-1-phosphate (S1P) related gene expression and sphingolipids in gut tissue, correlating with active disease. These markers normalize with remission, suggesting potential for monitoring therapy response.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Inflammatory bowel disease (IBD) is a growing concern in pediatric populations.
- Current IBD therapies target sphingosine-1-phosphate (S1P) receptors, but S1P metabolism and signaling in pediatric IBD are not well understood.
- Characterizing S1P-related gene expression and sphingolipid profiles in pediatric IBD is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate gene expression of proteins involved in sphingosine-1-phosphate (S1P) metabolism and signaling.
- To analyze sphingolipid levels in pediatric IBD patients.
- To correlate S1P-related gene expression and sphingolipid profiles with disease activity.
Main Methods:
- Recruitment of pediatric IBD patients and controls across four sites.
- Clinical scoring using PUCAI or PCDAI, and collection of colon biopsies during endoscopy.
- Quantitative real-time PCR (qRT-PCR) for gene expression and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for sphingolipid analysis in plasma and gut tissue.
Main Results:
- Significant upregulation of S1P synthesis (SPHK1, SPHK2), degradation (SGPL1), and signaling (S1PR1, S1PR2, S1PR4) genes in colon biopsies of IBD patients with moderate/severe symptoms compared to controls or those in remission.
- Elevated tissue levels of ceramide, dihydroceramide, and ceramide-1-phosphate (C1P) in pediatric IBD patients.
- Correlation between elevated S1P-related gene expression in colon tissue and active disease, with normalization in remission.
Conclusions:
- A distinct gene expression signature for S1P metabolism and signaling is associated with active pediatric IBD.
- High levels of pro-apoptotic and pro-inflammatory sphingolipids are present in the gut tissue of symptomatic pediatric IBD patients.
- Combined analysis of sphingolipid profiles and S1P-related gene signature may aid in monitoring therapeutic response in pediatric IBD.
Goal:
The aim of this study was to investigate gene expression levels of proteins involved in sphingosine-1-phosphate (S1P) metabolism and signaling in a pediatric inflammatory bowel disease (IBD) patient population.
Background:
IBD is a debilitating disease affecting 0.4% of the US population. The incidence of IBD in childhood is rising. Identifying effective targeted therapies that can be used safely in young patients and developing tools for selecting specific candidates for targeted therapies are important goals. Clinical IBD trials now underway target S1PR1, a receptor for the pro-inflammatory sphingolipid S1P. However, circulating and tissue sphingolipid levels and S1P-related gene expression have not been characterized in pediatric IBD.
Methods:
Pediatric IBD patients and controls were recruited in a four-site study. Patients received a clinical score using PUCAI or PCDAI evaluation. Colon biopsies were collected during endoscopy. Gene expression was measured by qRT-PCR. Plasma and gut tissue sphingolipids were measured by LC-MS/MS.
Results:
Genes of S1P synthesis (SPHK1, SPHK2), degradation (SGPL1), and signaling (S1PR1, S1PR2, and S1PR4) were significantly upregulated in colon biopsies of IBD patients with moderate/severe symptoms compared with controls or patients in remission. Tissue ceramide, dihydroceramide, and ceramide-1-phosphate (C1P) levels were significantly elevated in IBD patients compared with controls.
Conclusions:
A signature of elevated S1P-related gene expression in colon tissues of pediatric IBD patients correlates with active disease and normalizes in remission. Biopsied gut tissue from symptomatic IBD patients contains high levels of pro-apoptotic and pro-inflammatory sphingolipids. A combined analysis of gut tissue sphingolipid profiles with this S1P-related gene signature may be useful for monitoring response to conventional therapy.
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