Polycystin-2 expression is increased following experimental ischaemic renal injury.
BACKGROUND
Mutations in PKD2 account for 15% of patients with autosomal dominant polycystic kidney disease. Expression of the PKD2 protein, polycystin-2, is developmentally regulated, suggesting a major role for this protein during nephrogenesis. However, the regulation of polycystin-2 expression in the adult kidney has not been previously explored.


METHODS
We have utilized an established model of renal ischaemic injury to study polycystin-2 expression in adult rat kidney for up to 120 h following ischaemia.


RESULTS
Our results indicate that polycystin-2 expression is increased in the post-ischaemic kidney by up to 5-fold, with a peak in expression at 48 h reperfusion. This time course mirrored the increase in cell proliferation observed. In the non-ischaemic kidney, polycystin-2 expression was highest in distal nephron segments but faint proximal tubular staining was also observed. No expression was seen in glomeruli. In the ischaemic kidney, polycystin-2 expression was greatly increased but the increase in expression was not restricted to segments with the highest number of proliferating cells. Moreover, polycystin-2 was detectable mainly intracellularly following ischaemia. Consistent with this, polycystin-2 was completely sensitive to endoglycosidase H during renal recovery, suggesting that it remains largely retained within the endoplasmic reticulum under these conditions.


CONCLUSIONS
Our results provide the first evidence that polycystin-2 is increased following renal ischaemia, but show that this increase is not restricted to actively proliferating cells. The increase in polycystin-2 may relate instead to the process of cellular repair or differentiation following injury.
Zhao
Yan
Y
Sheffield Kidney Institute, Section of Human Metabolism, Division of Clinical Sciences (NGH), University of Sheffield, Sheffield, UK.
Haylor
John L
JL
Ong
Albert C M
AC
D000818:Animals; D019556:COS Cells; D002455:Cell Division / Q000502:physiology; D006031:Glycosylation; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000378:metabolism*; D050396:TRPP Cation Channels; D014018:Tissue Distribution
D008565:Membrane Proteins; D050396:TRPP Cation Channels