Background

Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker
of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and
mouse kidney cell line (TKPTS) to determine the signaling pathways that regulate netrin-1 production in response to injury.

Methods and Principal Findings

Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle
for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate,
cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time
RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1
production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug
induced netrin-1 mRNA translation increase without altering mRNA stability.

Conclusion

Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads
to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells.