Abstract: SA-PO600
Deciphering the Role of Angpt4-Tie2 Signaling in the Kidney
Session Information
- AKI: Other Mechanisms and Cell Cultures
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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.