SCUBE1, a novel developmental gene involved in renal regeneration and repair.

We have identified that a novel developmental gene and protein, SCUBE1, is expressed in endothelial cells and may play an important role in kidney regeneration. The temporal and spatial expression of SCUBE1 was determined in a mouse model of ischaemia-reperfusion (IR) injury at 3 days and 1, 3 and 6 weeks post-injury by immunofluorescence microscopy. In vitro analysis was used to examine SCUBE1 signalling in endothelial cells under conditions of cell stress using quantitative real-time polymerase chain reaction and immunofluorescence labelling. The media from cultured endothelial cells following SCUBE1 small interfering RNA (siRNA) transfection was used to assess the proliferation capacity of epithelial cells. Immunofluorescence confocal microscopy demonstrated that the SCUBE1 protein was localized to CD31-positive endothelial cells in IR kidneys during the resolution of tissue damage (3 weeks), but not in control animals. The peak expression of SCUBE1 following 3 weeks of IR injury was confirmed by reverse transcription-polymerase chain reaction. SCUBE1 mRNA and protein expression were detected in cultured endothelial cells under hypoxic conditions or serum starving. Furthermore, there was a significant decrease in epithelial cell proliferation following the addition of a supernatant derived from cultured endothelial cells following SCUBE1 siRNA gene silencing compared to control media. Our results indicate that SCUBE1 may be involved in the regulation of tubular cell proliferation and re-epithelialization during the resolution of kidney injury.