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Description
Many new drug treatments for multiple sclerosis (MS) target the Sphingosine 1-Phosphate (S1P) signaling pathway; to better understand how to properly treat MS, the baseline gene and protein expression in this signaling pathway is not well-understood. Furthermore, S1P receptor expression level changes in tissue sites where spontaneous and/or induced hemangiosarcomas (HSAs) are most commonly identified in CD-1 mice warrant investigation. In this study, we examined two of the receptor subtypes of S1P, which were S1pr1 and S1pr3. Due to past research from carcinogenicity studies, we hypothesized that both S1pr1 and S1pr3 would be highly expressed in the liver and spleen tissues, and moderately or minimally expressed in uterus and ovary. Notably, these tissues showed increased incidences of HSAs in two-year carcinogenicity studies with S1P agonists in CD-1 mice. Females and males, each n=5, were used to determine baseline expression of S1pr1 and S1pr3 as measured through mRNA and protein levels for the following tissues: liver, spleen, uterus, and ovary. Gene expression analysis revealed high expression of S1pr1 with minimal expression of S1pr3 in both male and female liver and spleen along with the uterus and ovary. S1PR1 protein was highly expressed in both male and female liver and spleen, while S1PR3 was highly expressed in liver of both males and females, but only moderately expressed in spleen. The uterus showed moderate expression of S1PR1, the ovary showed only negligible expression of S1PR1, and both tissues showed negligible expression of S1PR3. This work helped to establish the baseline expression profiles of two S1Ps in mouse skeletal muscle microvascular endothelial cell culture models and murine tissues, and these results can better inform future pharmacology and carcinogenicity study designs.
