The role of SLC34A2 in intestinal phosphate absorption and phosphate homeostasis

Abstract

There has recently been significant interest in the concept of directly targeting intestinal phosphate transport to control hyperphosphatemia in patients with chronic kidney disease. However, we do not have a complete understanding of the cellular mechanisms that govern dietary phosphate absorption. Studies in the 1970s documented both active and passive pathways for intestinal phosphate absorption. However, following the cloning of the intestinal SLC34 cotransporter, NaPi-IIb, much of the research focused on the role of this protein in active transcellular phosphate absorption and the factors involved in its regulation. Generation of a conditional NaPi-IIb knockout mouse has demonstrated that this protein is critical for the maintenance of skeletal integrity during periods of phosphate restriction and that under normal physiological conditions, the passive sodium-independent pathway is likely be the more dominant pathway for intestinal phosphate absorption. The review aims to summarise the most recent developments in our understanding of the role of the intestine in phosphate homeostasis, including the acute and chronic renal adaptations that occur in response to dietary phosphate intake. Evidence regarding the overall contribution of the transcellular and paracellular pathways for phosphate absorption will be discussed, together with the clinical benefit of inhibiting these pathways for the treatment of hyperphosphatemia in chronic kidney disease.

A guide to plasma membrane solute carrier proteins

“…Although SLC34A3 internalization is similarly induced by PTH, the response is markedly slower than that of SLC34A1 [403]. SLC34A2 is expressed in many different organs, such as the small intestine, where it provides over 90% of the sodium-dependent cellular absorption of phosphate [397,398,404].…”

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

“…The second pathway for intestinal P i absorption is mediated primarily by the sodium-dependent phosphate transport protein 2b, NPT2b (encoded by SLC34A2 ). To a lesser extent, this transcellular transport is also mediated by the type 3 sodium-dependent transporters, PIT1 (encoded by SLC20A1 ) and PIT2 (encoded by SLC20A2 ), although the role of the latter is not clear [ 21 , 33 ]. This high affinity and saturable transporter-mediated pathway is present in the duodenum and jejunum [ 34 , 35 , 36 , 37 ], is stimulated by 1,25-dihydroxyvitamin D [1,25(OH) 2 D, or calcitriol], and accounts for 30% of intestinal P i absorption when phosphorus is abundant in the diet [ 21 , 34 , 38 , 39 ].…”

“…This effect occurs at the transcriptional level [ 120 ]. These molecules and their effects on intestinal P i absorption are described in further detail in several excellent reviews [ 31 , 33 , 118 ].…”

GutSelf: Interindividual Variability in the Processing of Dietary Compounds by the Human Gastrointestinal Tract

“…SLC9 Na + /H + exchangers (as SLC9A3) drive electroneutral NaCl absorption, whereas a Na + /H + antiporter (NHE2, NHE3, and NHE8 isoforms) has also been identified . Phosphate intake may occur through an apical Na + ‐phosphate cotransporter driven by NaPi‐IIb (SLC34A4) …”