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Institute of Physiology

Intestinal transport of phosphate

Nati Hernando (see Short CV (PDF, 61 KB)) PubMed)

Graphic

Background We are interested in a better understanding of the mechanisms that mediate intestinal absorption of phosphate. This topic is of major relevance since dietary intake of phosphate has sharply increased in recent years and hyperphosphatemia associates with cardiovascular disease and mortality.

 

Earlier studies indicated that transport of phosphate across the intestinal epithelia involves active and passive processes, with the influx across the apical membrane of enterocytes representing the active step. The Na+-coupled phosphate cotransporter NaPi-IIb mediates this active step, whereas little is known about the potential role of other transporters (i.e PiT1/2) and the relative contribution of the passive/paracellular transport. NaPi-IIb is a member of the Slc34 family of solute carriers, and its abundance at the apical membrane of enterocytes is regulated, among other factors, by vitamin D3 and dietary Pi.

 

To study the contribution of NaPi-IIb to intestinal absorption of phosphate, we have generated a mouse model with intestinal-specific depletion of NaPi-IIb. Depletion of NaPi-IIb results in a minor increase in intestinal loss of phosphate, suggesting that other mechanism(s) must be involved in intestinal absorption of phosphate. Therefore, our aim is to investigate the nature of these additional mechanism(s), taking advantage of the fact that the NaPi-IIb-deficient model would provide us with tissue samples devoid of the major, if not only, active component of the intestinal absorption of Pi. 

 

Topics

  • Mapping the intestinal distribution of active and passive/paracellular transport of phosphate
  • Mapping the intestinal distribution of known phosphate transporters
  • Mapping the composition of intestinal tight junctions
  • Study the contribution of NaPi-IIb to basal and regulated intestinal absorption of phosphate
  • Study the contribution of other transporters to basal and regulated intestinal absorption of phosphate

 

Collaborations

For some of the projects outline above, our group collaborates with the labs of Dr. Günzel from the Institute of Clinical Physiology, at the Charite Campus Benjamin Franklin-Berlin (Germany) and of Dr. M. Bleich from the Institute of Physiology at the Christian Albrechts University of Kiel (Germany), as well as with Dr. ÅL Jönsson from the University Hospital of Aarhus (Denmark).