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Updated: Jun 23, 2026
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Segment-specific expression of netrin-1 receptors in normal and ischemic mouse kidney
1Division of Nephrology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
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.
Insights
Netrin-1 receptors UNC5B and UNC5C are located in specific kidney tubule segments, while neogenin is widespread. Their mRNA levels decrease after kidney injury, suggesting localized roles in renal health and disease.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Netrin-1 protects kidneys from ischemia reperfusion injury by reducing apoptosis and promoting cell growth.
- Netrin-1 acts via cell-surface receptors including DCC, neogenin, UNC5 homologues, and integrins.
- Kidneys express UNC5B, UNC5C, and neogenin mRNA, but their precise locations are unknown.
Purpose of the Study:
- To determine the intrarenal localization of netrin-1 receptors (UNC5B, UNC5C, neogenin).
- To investigate changes in receptor expression following ischemia reperfusion injury.
Main Methods:
- Real-time RT-PCR and immunohistochemistry were used to analyze netrin-1 receptor expression.
- Expression was examined in normal kidneys and kidneys subjected to ischemia reperfusion injury.
Main Results:
- UNC5B expression is confined to proximal tubule S3 segments; UNC5C is restricted to distal tubules.
- Neogenin is expressed throughout the nephron, including glomeruli, and localized to the basolateral membrane of tubular cells.
- While protein expression remained unchanged, mRNA levels of UNC5B, UNC5C, and neogenin were significantly downregulated post-injury.
Conclusions:
- Netrin-1 receptors exhibit segment-specific expression within the nephron.
- These distinct localizations suggest specialized functions for netrin-1 receptors in different kidney segments.
- Differential regulation of receptor mRNA following injury warrants further investigation into their roles in kidney pathophysiology.
