Renal cilia display length alterations following tubular injury and are present early in epithelial repair

Abstract

Background: Renal cilia are flow sensors that are required for the maintenance of normal kidney architecture. Defects in this organelle are frequently associated with polycystic kidney disease, but the role of renal cilia during acute tubular injury has not been investigated.

Methods: We have analysed the presence and dimensions of renal cilia following renal ischaemia-reperfusion and ureteral obstruction injury in the mouse, and related these results to injury and repair of the renal tubule. The expression of genes encoding cilium-localized proteins was measured following ischaemia-reperfusion injury.

Results: Ischaemia-reperfusion injury was demonstrated to affect the length of cilia in the renal tubule and duct. The average length of renal cilia in the proximal tubule decreases 1 day (2.8 +/- 0.4 microm) and 2 days (3.0 +/- 0.2 microm) after injury, as compared to the control uninjured proximal tubule (4.2 +/- 0.3 microm). Later in the injury and repair process at 4 and 7 days, the average length of cilia increases in both the proximal (7 days = 6.2 +/- 0.3 microm) and distal tubule/collecting duct (4 days = 4.4 +/- 0.3 microm; 7 days = 5.5 +/- 0.4 microm; control 2.5 +/- 0.1 microm). The expression level of genes encoding cilium-localized products did not correlate with the increase in cilium length following ischaemia-reperfusion injury. Ureteral obstruction for 8 days also caused lengthening (8 days UUO = 5.8 +/- 0.3 microm; control 2.5 +/- 0.1 microm) of renal cilia in the distal tubule/collecting duct. During the repair process that follows ischaemia-reperfusion injury, cilia were present on the dedifferentiated cells that proliferate and adopt an epithelial phenotype to facilitate the repair of the ischaemic renal tubule.

Conclusions: We propose roles for the renal cilium in responding to changes in the renal environment caused by injury, and in the repair process that re-establishes the epithelial layer of the damaged renal tubule.