Sphingosine-1-phosphate/S1P Receptors Signaling Modulates Cell Migration in Human Bone Marrow-Derived Mesenchymal Stem Cells

Abstract

The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs) in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a Gi/extracellular regulated protein kinases 1/2- (ERK1/2-) dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK) pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR's activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration.

Sphingosine-1-Phosphate Mediates Fibrosis in Orbital Fibroblasts in Graves' Orbitopathy

“…Expression levels of profibrotic proteins-collagen Ia, fibronectin, and a-SMA-in TGF-b-stimulated GO orbital fibroblasts with or without pretreatment with S1PR (W146, JTE013, or FTY720) or SphK1 (5C) blockers were evaluated by Western blotting as described previously. [21][22][23][24] While TGF-b-induced Sphingosine-1-Phosphate Mediates Fibrosis in GO IOVS j May 2017 j Vol. 58 j No.…”

The effect of carboxylated nanodiamond (cNDs) on the migration of HepG2 cells

“…Cell migration was measured using a transwell assay kit with 8‐mm pores as previously described . The cells were suspended in serum‐free DMEM medium containing different concentration cNDs by using 1% FBS as a chemoattractant.…”

Sphingosine-1-Phosphate Is a Crucial Signal for Migration of Retina Müller Glial Cells

“…To evaluate whether S1P activated S1P1 and/or S1P3 to regulate glial cell migration, pure glial cultures were incubated in DMEM for 24 hours and, after making the scratch, treated either with W146, a S1P1 antagonist, 23 or with BML-241, a S1P3 antagonist, 24,25 or with their vehicles. Working solutions (1 mg/mL) were prepared in dimethyl sulfoxide (DMSO) (W146) or ethanol (BML-241) and then added at a 10-lM concentration to the cultures.…”