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Kidney Week

Abstract: SA-PO600

Deciphering the Role of Angpt4-Tie2 Signaling in the Kidney

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Tarjus, Antoine, 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
  • Quaggin, Susan E., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States

Group or Team Name

  • Quaggin lab
Background

The angiopoietin-Tie2 signaling pathway is fundamental for vascular development and has been linked to numerous kidney diseases including diabetic nephropathy and sepsis-related AKI. The pathway is composed of two receptors, Tie1 and Tie2, and three ligands, Angiopoiein-1, Angiopoietin-2 and Angiopoietin-4 (Angpt-4). Among the ligands, Angpt-4 has been poorly characterized. While Angpt4 has been suggested to act as a Tie2 agonist and seems to be highly regulated by hypoxia, its physiological role remains elusive. Moreover, the study of Angpt-4 function is currently challenging due to the lack of knockout transgenic model. In order to decipher its physiological role, we have developed a new Angpt4 mouse model.

Methods

We generated a new reporter and conditional allele for Angpt4 in mice. Using the X-gal chromogenic substrate of the β-galactosidase, this model allows us to characterize high-resolution expression pattern of Angpt-4. To identify the cell type expressing Angpt-4, we performed immunohistochemical staining on tissue sections using antibody coupled with the alkaline phosphatase enzyme. Global and timed deletion of Angpt4 was accomplished using ubiquitous and tetON inducible Cre-deletor lines.

Results

X-gal staining reveals strong expression restricted to the vasculature of organs including the kidney, adrenal glands, gonads, and mesentery. In the kidney, X-gal staining is found in the renal and interlobular arteries. Using an antibody against Transgelin (SM22), a marker of smooth muscle cells, we show Angpt-4 co-localizes with vascular smooth muscle cells in the kidney. Global KO mice survive to birth and renal function testing is underway.

Conclusion

Our data demonstrate a highly specific vascular pattern of expression for Angpt-4 in smooth muscle cells of the vascular wall. These observations suggest that Angpt-4 may have a role in arterial function with potential impact in the pathology of renal ischemia as Angpt-4 has been shown to be regulated by hypoxia.