Segment-specific expression of netrin-1 receptors in normal and ischemic mouse kidney

Background/Aims: Netrin-1 plays a key role in the prevention of ischemia reperfusion induced kidney injury by suppressing apoptosis and increasing epithelial cell proliferation. Netrin-1 binds to cell-surface receptors, which include members of the deleted in colorectal cancer (DCC and neogenin), UNC5 homologue and integrin families, to mediate its actions. Kidney is known to express three netrin-1 receptors mRNA (UNC5B, UNC5C and neogenin) abundantly. However, the intrarenal localization of these receptors is unknown. Methods: We analyzed netrin-1 receptor expression in normal kidney and after ischemia reperfusion injury by real-time RT-PCR and immunohistochemistry. Results: We show that UNC5B expression is restricted to S3 segments of proximal tubules, whereas UNC5C expression is restricted to distal tubules. There was no expression of UNC5B and UNC5C in the glomerulus. Neogenin is expressed in all segments of the nephron including the glomerulus. Neogenin expression was restricted to the basolateral membrane in tubular epithelial cells. The expression patterns of UNC5B, UNC5C and neogenin were not altered after ischemia reperfusion injury. In contrast to protein expression, mRNA expression was significantly down-regulated after ischemia reperfusion injury of the kidney. Conclusion: Netrin-1 receptors were expressed in specific segments and may have differential functions in different segments of the nephron.