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: TH-PO866

Apelinergic System in the Kidney: Implications for Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Müller, Tilman, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Kalea, Anastasia Z., University College London, London, United Kingdom
  • Haque, Syed K., American Laboratory Consultant LLC, Park Ridge, Illinois, United States
  • Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
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