Abstract: SA-PO273
Expression and Distribution of Different Protein Kinase A Isoforms in Healthy and Diseased Kidneys
Session Information
- Diabetic Kidney Disease: Basic - 2
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Prueschenk, Sally Sabrina Theresa, Universitat Regensburg Fakultat fur Chemie und Pharmazie, Regensburg, Bayern, Germany
- Taylor, Susan, University of California San Diego School of Medicine, La Jolla, California, United States
- Schlossmann, Jens, Universitat Regensburg Fakultat fur Chemie und Pharmazie, Regensburg, Bayern, Germany
Background
Diabetic nephropathy (DN) is a major universal problem caused by hyperglycaemia and might require dialysis or renal replacement. Still, the signalling events causing diabetic kidney disease and the effective treatment options are poorly understood. Alterations in the signalling of cyclic nucleotides and its regulated kinases might be involved in the development of this disease. Protein kinase A (PKA) signalling pathways are known to modulate extracellular matrix metabolism in diabetic kidneys. Multiple isoforms of PKA regulatory and catalytic subunits exist, leading to functional specificities of this kinase. However, localization of the specific PKA subunits, as well as other signalling proteins involved in this pathway, still need to be explored comprehensively. PKA, which is activated through cAMP, was described to exert antifibrotic effects and might therefore be important in prevention of fibrosis or DN. The aim of our project is to get an overview about distribution pattern of different PKA subunits in various cell types of the kidney. Furthermore, amount of PKA expression in healthy and diabetic kidneys is compared.
Methods
Type 1 diabetes was induced with streptozotocin in wild-type (WT) and endothelial NOS knockout (eNOS-KO) mice for 12 weeks. Kidneys were analysed by immunohistochemistry and stained with specific antibodies for different PKA subunits and markers for specialized renal cell types. Amount of catalytic subunit expression was quantified and compared between healthy and diabetic kidneys.
Results
The catalytic subunits PKA-Cα and PKA-Cβ reveal a different expression pattern in different segments of the kidney and interestingly the intracellular localization varies. Furthermore, PKA-Cα seems to be the predominant isoform in a lot of cell types. We also observe an altered amount of catalytic subunit expression in diabetic kidneys compared to healthy kidneys.
Conclusion
Our data show that catalytic subunits of PKA reveal a different distribution pattern in specialized cell types of the kidney as well as a different intracellular localization. Furthermore, the amount of catalytic subunit expression varies between healthy and diabetic kidneys. Therefore, PKA might play an important role in pathophysiology of DN and targeting the PKA signalling pathway could be a potential treatment approach.
Funding
- Government Support – Non-U.S.