ABSTRACT
Inorganic phosphate (Pi) is the second most abundant inorganic ion in the body. Since abnormalities in Pi metabolism are risk factors for various diseases, serum Pi levels are strictly controlled. Type-III sodium-dependent Pi transporters, PiT-1 (encoded by SLC20A1) and PiT-2 (encoded by SLC20A2), are distributed throughout the tissues of the body, including the central nervous system, and are known to be responsible for extracellular to intracellular Pi transport. Platelet-derived growth factor (PDGF) is a major growth factor of mesenchymal cells. PDGF-BB, a homodimer of PDGF-B, regulates intracellular Pi by increasing PiT-1 expression in vascular smooth muscle cells. However, the effects of PDGF-BB on Pi transporters in neurons have yet to be reported. Here, we investigated the effect of PDGF-BB on Pi transporters in human neuroblastoma SH-SY5Y cells. PDGF-BB did not induce SLC20A1 mRNA expression, but it increased the intracellular uptake of Pi via PiT-1 in SH-SY5Y cells. Among the signaling pathways associated with PDGF-BB, AKT signaling was shown to be involved in the increase in Pi transport. In addition, the PDGF-BB-induced increase in Pi mediated neuroprotective effects in SLC20A2-suppressed cells, in an in vitro model of the pathological condition found in idiopathic basal ganglia calcification. Moreover, the increase in Pi uptake was found to occur through promotion of intracellular PiT-1 translocation to the plasma membrane. Overall, these results indicate that PDGF-BB exerts neuroprotective effects via Pi transport, and they demonstrate the potential utility of PDGF-BB against abnormal Pi metabolism in neurons.