Abstract: TH-PO274

AKI Stimulates Inflammation Associated Lymphangiogenesis

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Bowhay, Sarah Ann, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Agarwal, Anupam, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Traylor, Amie, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Zarjou, Abolfazl, University of Alabama at Birmingham , Birmingham, Alabama, United States
Background

The lymphatic system is crucial for maintaining fluid balance, transporting lipids, and aiding in immune function. The functions of the lymphatic system are further accentuated during pathological conditions such as inflammation, the latter a key component of acute kidney injury (AKI). Inflammation induces lymphangiogenesis through expression of vascular endothelial growth factors (VEGFs), particularly VEGF-C, VEGF-D, and their receptor VEGF-R3. While recent studies have shown lymphangiogenesis to be an active participant in a number of inflammatory diseases, very little is known about the role of the lymphatic system and more importantly, lymphangiogenesis, in the pathogenesis of AKI. Based on the prominent role of lymphangiogenesis in various inflammation induced disease models, this delicate and crucial pathway could serve as a novel target to be exploited for therapeutic interventions in AKI.

Methods

To study the role of lymphangiogenesis in the pathophysiology of AKI, we induced renal injury in mice via bilateral ischemia-reperfusion injury (I/R), a well characterized model of AKI and measured lymphatic vessel content as well as mRNA and protein levels of growth factors and inducers of lymphangiogenesis.

Results

We observed increased lymphatic vessel content in kidneys of mice that had undergone I/R compared to uninjured controls via LYVE1 (a cell surface receptor on lymphatic endothelial cells) immunohistochemistry. RT-PCR analysis revealed increased levels of lymphatic markers, LYVE1 and Podoplanin in kidneys 7 days after I/R. We also observed increased VEGF-R3 protein levels after injury peaking at day 3 post I/R in kidney lysates. ELISA analysis of VEGF-C levels showed a decrease in kidney VEGF-C with a simultaneous increase in serum levels of VEGF-C. VEGF-C protein was also detected in the urine at day 1 post I/R. VEGF-C immunofluorescence staining revealed expression in proximal tubule cells in uninjured kidneys. After I/R, VEGF-C is seen in the apical side of proximal tubule cells. This together suggests a mechanism in which VEGF-C is secreted from the tubules into the blood and urine following injury.

Conclusion

These results suggest that lymphangiogenesis is stimulated in kidneys after AKI and may represent a target for intervention in the pathogenesis of AKI.