Nephrol Dial Transplant (2002) 17: 2138-2144
© 2002 European Renal Association-European Dialysis and Transplant Association
Polycystin-2 expression is increased following experimental ischaemic renal injury
Sheffield Kidney Institute, Section of Human Metabolism, Division of Clinical Sciences (NGH), University of Sheffield, Sheffield, UK
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.
Keywords: ADPKD; PKD2; polycystic kidney disease; polycystin-2; renal ischaemia
Correspondence and offprint requests to: Dr Albert CM Ong, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK. Email: a.ong{at}sheffield.ac.uk
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  M. Y. Chang, E. Parker, S. Ibrahim, J. R. Shortland, M. E. Nahas, J. L. Haylor, and A. C. M. Ong Haploinsufficiency of Pkd2 is associated with increased tubular cell proliferation and interstitial fibrosis in two murine Pkd2 models Nephrol. Dial. Transplant., August 1, 2006; 21(8): 2078 - 2084. [Abstract] [Full Text] [PDF]
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