Kidney Week

Abstract: TH-PO866

Apelinergic System in the Kidney: Implications for Diabetic Kidney Disease

Session Information

• Diabetic Kidney Disease: Basic - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Müller, Tilman, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Tilman Müller,

• Kalea, Anastasia Z., University College London, London, United Kingdom

Anastasia Z. Kalea,

• Haque, Syed K., American Laboratory Consultant LLC, Park Ridge, Illinois, United States

Syed K. Haque,

• Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Minghao Ye,

• Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Jan Wysocki,

• Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Daniel Batlle,

Background

The bioactive peptides of the apelinergic system and its receptor APJ may play a protective role in cardiovascular and diabetic kidney disease (DKD). We examined the glomerular localization of APJ in the db/db mice and the effect of hyperglycemia and Angiotensin II on APJ mRNA in cultured podocytes. The impact of AT1R blockade on APJ expression was also studied in db/db mice.

Methods

Obese db/db mice of 8wk of age were used as a model of type 2 diabetes and their littermates db/m served as non diabetic controls. mRNA for APJ and propreapelin was measured by real time PCR; protein expression for APJ was studied by western blot on kidney lysates. Immunohistochemistry and immunofluorescence microscopy was used to localize APJ in the kidney.

Results

APJ co-localized with podocyte but not endothelial cell markers. In podocytes stimulated with Pyr¹Apelin-13 a change in the phosphorylation status of the signaling proteins, AKT, ERK and p70S6K, was observed with an increase 15 min after stimulation. Apelin-13 decreased activity of Caspase-3 in podocytes after high glucose exposure reflecting an anti-apoptotic effect of APJ stimulation. In podocytes, APJ mRNA was down regulated in high glucose, and exposure to angiotensin II led to a further significant decrease in APJ mRNA. APJ and propreapelin mRNA in kidneys from db/db mice were decreased when compared to db/m controls; treatment with the specific AT1R blocker Telmisartan significantly increased APJ mRNA and propreapelin levels.

Conclusion

APJ is mainly localized in podocytes and in this cell type its activation by Apelin-13 abolishes the proapoptic effect of high glucose, suggesting a potential therapeutic role of apelin and emerging agonists with extended half- life in DKD. In addition, AT1 blockade with Telmisartan resulted in an increase in APJ mRNA and propreapelin levels in db/db mice suggesting a link of the apelinergic system and the AT1 receptor

Funding

• NIDDK Support