Abstract
Sphingosine-1-phosphate (S1P) is a highly potent sphingolipid metabolite, which controls numerous physiological and pathological process via its extracellular and intracellular functions. The breast is mainly composed of epithelial cells (mammary gland) and adipocytes (stroma). Adipocytes play an important role in regulating the normal functions of the breast. Compared to the vast amount studies on breast epithelial cells, the functions of S1P in breast adipocytes are much less known. Thus, in the current study, we used human preadipocyte cell lines SGBS and mouse preadipocyte cell line 3T3-L1 as in vitro models to evaluate the effects of S1P on cell viability, differentiation, and gene expression in adipocytes. Our results showed that S1P increased cell viability in SGBS and 3T3-L1 preadipocytes but moderately reduced cell viability in differentiated SGBS and 3T3-L1 adipocytes. S1P was also shown to inhibit adipogenic differentiation of SGBS and 3T3-L1 at concentration higher than 1000 nM. Transcriptome analyses showed that S1P was more influential on gene expression in differentiated adipocytes. Furthermore, our network analysis in mature adipocytes showed that the upregulated DEGs (differentially expressed genes) were related to regulation of lipolysis, PPAR (peroxisome proliferator-activated receptor) signaling, alcoholism, and toll-like receptor signaling, whereas the downregulated DEGs were overrepresented in cytokine-cytokine receptor interaction, focal adhesion, starch and sucrose metabolism, and nuclear receptors pathways. Together previous studies on the functions of S1P in breast epithelial cells, the current study implicated that S1P may play a critical role in modulating the bidirectional regulation of adipocyte-extracellular matrix-epithelial cell axis and maintaining the normal physiological functions of the breast.
Highlights
Sphingosine-1-phosphate (S1P) is a highly potent sphingolipid metabolite which tightly controls various physiological and pathological processes via its extracellular and intracellular functions [1,2]
Our network analysis in mature adipocytes showed that the upregulated Differentially expressed genes (DEGs) were related to regulation of lipolysis, PPAR signaling, alcoholism, and toll-like receptor signaling, whereas the downregulated DEGs were overrepresented in cytokine–cytokine receptor interaction, focal adhesion, starch and sucrose metabolism, and nuclear receptors pathways
For SGBS preadipocytes, cell viability was statistically significantly increased from 12% at 1000 nM to 28% at 5000 nM after 24 h of S1P treatment and by 10% (p < 0.05) at 2500 nM and 20% at 5000 nM (p < 0.05) after 48 h of S1P treatment
Summary
Sphingosine-1-phosphate (S1P) is a highly potent sphingolipid metabolite which tightly controls various physiological and pathological processes via its extracellular and intracellular functions [1,2]. The breast is a highly specialized female exocrine organ responsible for producing milk to feed offspring It is structurally divided into ductal epithelium and connective tissue stroma [13]. Limited previous studies showed that S1P inhibits the differentiation of mouse preadipocyte 3T3-L1 cells at concentration higher than 0.5 μM [21]; and modulates adipocyte hypertrophy [22,23,24] and proinflammation response [25]. A recent study showed that the level of S1P was about 10 times higher in the interstitial fluid (layer of fluid surrounding the mammary gland) than the mammary gland itself [31] This implicates that S1P plays a critical role in regulating mammary ductal epithelium, stromal adipocyte tissue and their mutual communications. The number of gene regulated by S1P was significantly increased in the differentiated adipocytes
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