Type III sodium-dependent inorganic phosphate transporters are required for the phenotypes in human brain...

Inorganic phosphate (Pi) homeostasis in the brain is critical for the development of primary brain calcification (PBC). In the brains of patients with PBC, calcification occurs in the cerebral small vessels, and it is primarily caused by mutated SLC20A2, a gene that encodes a type III Pi transporter. A previous study founded that the SLC20 family, which includes SLC20A1 and SLC20A2, contributes to Pi homeostasis in the central nervous system. However, the impact of these Pi transporters on the brain vessel phenotype remains unknown. Thus, in this study, we aimed to investigate the effect of SLC20A1 or SLC20A2 depletion on the phenotype of human brain microvascular endothelial cells (hBMECs). We assessed the primary phenotypes of vascular endothelial cells, such as proliferation, tube formation, and VE-cadherin expression. The results showed that hBMECs silenced for SLC20A1 or SLC20A2 had decreased proliferative and angiogenic ability, as well as VE-cadherin expression. The intracellular Pi concentration ([Pi]_i) remained constant in SLC20A1-silenced hBMECs whereas it increased in SLC20A2-silenced cells. Tube formation ability was no change even at 3 mM, a concentration higher than [Pi]_i which was increased in SLC20A2-silenced hBMECs. Thus, increased [Pi]_i in SLC20A2-silenced hBMECs may have a small impact on phenotypic changes. In conclusion, abnormalities in Pi homeostasis caused by SLC20A2 depletion were suggested to play a minor role in PBC endothelial pathology.