Tissue Non-Specific Alkaline Phosphatase May Be a Function-Related Marker in Renal Proximal Tubular Epithelia and in Vascular Endothelia as It Is in Osteoblasts

Abstract

Tissue non-specific alkaline phosphatase (TN-AP) is a multifunctional phosphatase and has a variety of substrates in vitro. In adults, TN-AP is highly expressed in osteoblasts, renal proximal tubular epithelia and vascular endothelia. In osteoblasts, it is well known that TN-AP plays an important role in bone mineralization. Considering its many activities in vitro, we hypothesize that TN-AP also plays a role in regulating cellular activities in renal proximal tubular epithelia and vascular endothelia. By using a stable gene transfection technique, we transfected two cell lines with a rat TN-AP gene, one renal proximal tubule-like (LLC-PK1), another vascular endothelia-like (Py-4-1). The effect of TN-AP expression was cell specific. In Py-4-1 cells, the forced TN-AP expression stimulates cellular behaviours associated with terminal differentiation. This suggests that in vivo AP expression in certain vascular endothelia may mark a terminal-differentiated subpopulation with less angiogenic potential. While, in LLC-PK1 cells, the forced TN-AP expression inhibited cellular transport function as demonstrated by delayed dome formation. By inference, TN-AP expression in renal proximal tubule in vivo should have a regulatory role in cellular transport. Our data suggest that TN-APs have roles as function-related markers in renal proximal tubular epithelia and vascular endothelia.