Proteases in Plasma and Kidney of dbdb Mice as Markers of Diabetes-Induced Nephropathy

Abstract EN

Db/db mice are overweight, dyslipidemic and develop diabetic complications, relevant for similar complications in human type 2 diabetes.

We have used db/db and db/+ control mice to investigate alterations in proteinase expression and activity in circulation and kidneys by SDS-PAGE zymography, electron microscopy, immunohistochemistry, Western blotting, and in situ zymography.

Plasma from db/db mice contained larger amounts of serine proteinases compared to db/+ mice.

Kidneys from the db/db mice had a significantly larger glomerular surface area and somewhat thicker glomerular basement membranes compared to the db/+ mice.

Furthermore, kidney extracts from db/+ mice contained metalloproteinases with Mr of approximately 92000, compatible with MMP-9, not observed in db/db mice.

These results indicate that higher levels of serine proteinases in plasma may serve as potential markers for kidney changes in db/db mice, whereas a decrease in MMP-9 in the kidney may be related to the glomerular changes.