ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO193

Disruption of Angiopoietin-TIE2 Signaling Causes Loss of Ascending Vasa Recta and Cystic Kidney Disease

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Kenig-Kozlovsky, Yael, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Scott, Rizaldy P., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Onay, Tuncer, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Carota, Isabel Anna, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Thomson, Benjamin R., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Quaggin, Susan E., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Gil, Hyea Jin, Northwestern University, Chicago, Illinois, United States
Background

The renal vasculature is a complex and highly specialized vascular network. Heterogeneous segments of the renal vasculature differ in their anatomical structure, expression of endothelial markers and their role in renal function. The specialized capillaries of the ascending and descending vasa recta form the vascular bundles of the outer medulla, which play a key role in countercurrent exchange and urine concentration. In this study we sought to determine how the angiopoietin-Tie2 signaling pathway, which is known to be important in development and remodeling of blood and lymphatic vessels, affects the complex renal vasculature.

Methods

Using a Cre-based inducible gene targeting strategy we deleted Angpt1, Angpt2, and Tie2 at late gestational age in the mouse in order to overcome null mutant embryonic lethality.

Results

Compound deletion of Angpt1 and Angpt2 or Tie2 at late gestation age, leads to marked reduction in density of the vascular bundles and medullary capillary plexus, due largely to loss of the ascending vasa recta. Interestingly, we discovered that the ascending vasa recta (AVR) are “hybrid” vessels, which co-express blood (CD34, endomucin) and lymphatic markers (Prox1, VEGFR3). Loss of AVR in mutant animals leads to urine concentration defects with high urine output and low urine osmolality. As early as postnatal day P2 mutant animals develop renal cysts in the outer medulla. Cells lining the cysts do not express epithelial or vascular (blood and lymphatic) markers but do express several molecular markers of myofibroblasts including vimentin, calponin, SM-22α, and α –SMA.

Conclusion

Our results show for the first time the presence of “hybrid” vessels in the kidney that rely on Angpt-Tie2 signaling to develop. Furthermore, our data show that loss of AVR leads to dramatic cysts and renal insufficiency, underscoring the key functional role vasa recta play in draining interstitial fluid from the medulla that lacks classic lymphatic circulation.

Funding

  • Other NIH Support