Expression of protein kinase A catalytic subunits in healthy and diseased mouse kidneys.

Abstract

Diabetic nephropathy (DN) is characterized by a decline in renal function resulting from hyperglycaemia and is often requiring dialysis or renal transplantation. Yet, the signalling events causing DN and the effective treatment options are poorly understood. Changes in the signalling of cyclic nucleotides and their regulated kinases are hypothesized to be involved in its development. Protein kinase A (PKA) signalling pathways are known to modulate extracellular matrix metabolism and exert antifibrotic effects. Multiple isoforms of PKA regulatory and catalytic subunits exist, leading to functional specificities of the kinase arising from different combinations of these isoforms. However, localization of the specific PKA subunits, as well as other signalling proteins involved in this pathway, still need to be explored comprehensively. To gain an overview about PKA distribution, kidneys were analysed by immunohistochemistry and stained for different PKA subunits. Type 1 diabetes was induced by streptozotocin in wildtype (WT) and endothelial NOS knockout (eNOS-KO) mice. The catalytic subunit expression was quantified and compared between healthy and diabetic kidneys. Analysis of expression patterns of the PKA catalytic subunits Cα and Cβ reveal differences across segments of the kidney and in intracellular localization. Cα exhibited ubiquitous expression in all renal cell types. In contrast, Cβ only shows a high expression in proximal tubules, while its expression in other segments is comparatively weak. No significant changes in Cα or Cβ expression are detectable in diabetic mice or eNOS-KO mice compared to WT mice.