A 50-Hz magnetic-field exposure promotes human amniotic cells proliferation via SphK–S1P–S1PR cascade mediated ERK signaling pathway

Extremely low-frequency electromagnetic fields (ELF-EMFs) present a kind of common non-ionizing radiation in public and occupational environments. Previous studies have suggested that ELF-EMF exposure might have a potential impact on co-carcinogenesis and the progression of tumorigenesis by inducing cell proliferation. However, the underlying mechanisms remain largely unknown. In this study, we investigated the possible role of the sphingosine-1-phosphate (S1P)-related pathway in regulating cell proliferation induced by 50-Hz, 0.4-mT magnetic-field (MF) exposure. The results showed that MF exposure significantly promoted sphingosine kinase 1 (SphK1) activity, and that inhibition of the SphK1–S1P–S1P receptor (S1PR) pathway could remarkably reverse MF-induced cell proliferation. Additionally, we could infer indirectly from an exogenous-S1P experiment that MF-induced S1P might act on S1PR1/3 in a paracrine and/or autocrine manner to mediate the proliferation effect. Notably, although the MF activated the extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) pathways, the SphK1–S1P–S1PR1/3 cascade regulated MF-induced proliferation by activating the ERK rather than the Akt pathway. Taken together, the findings of this study indicated that the SphK1–S1P–S1PR1/3 cascade played an important role in MF-induced proliferation by mediating the ERK signaling pathway, which could bring new insights into understanding and preventing the adverse effects of MFs. The signaling pathway model of 50-Hz MF-induced cell proliferation through the SphK–S1P–S1PR–ERK cascade in FL cells. MF: magnetic field; SphK: sphingosine kinase; Sph: sphingosine; S1P: sphingosine-1-phosphate; S1PR: sphingosine-1-phosphate receptor. [Display omitted] •A 50-Hz 0.4-mT magnetic field promoted human amniotic cells proliferation.•MF exposure increased the activity of SphK1.•MF exposure mediated the cell proliferation effect through S1PR1 and S1PR3 in an “inside-out” manner.•The MF-activated SphK1–S1P–S1PR1/3 axis mediated the ERK pathway and eventually led to cell proliferation.