Proteases in plasma and kidney of db /db mice as markers of diabetes-induced nephropathy
ForfatterHadler-Olsen, Elin Synnøve; Winberg, Jan-Olof; Reinholt, Finn P.; Larsen, Terje; Uhlin-Hansen, Lars; Jenssen, Trond Geir; Berg, Eli; Kolset, Svein Olav
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.
SiteringISRN Endocrinology (2011), Article ID 832642, 10 pages
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