Abstract P637: Pigment Epithelium Derived Factor (PEDF) Deficiency Increases Blood Pressure And Accentuates Glomerular Pathology In Diabetic Mice
Pigment Epithelium Derived Factor (PEDF) encoded by SERPINF1 gene has potent anti-angiogenic and cytoprotective activities. It has been reported that PEDF protein levels are reduced in the kidneys of rodents with experimentally induced diabetes. However the effect of PEDF on blood pressure has not been elucidated. Here, we used SERPINF1 KO mice to examine the impact of PEDF deficiency on kidney pathology and blood pressure in the STZ-induced mouse model of diabetes.
Twelve weeks after diabetes induction by STZ, SERPINF1 KO mice showed exacerbated glomerular damage with ~ 2-fold increase in mesangial matrix (2.8±0.14 vs. 1.2±0.14 arbitrary units, p<0.01) and ~ 20% decrease in podocyte counts (8.2±0.0.4 vs. 9.7±0.2 podocytes/glomerulus, p<0.01) compared to the wild type controls. Of note, STZ-treated SERPINF1-/- mice displayed elevated systolic blood pressure (SBP) (127±4 vs. 109±4 mmHg, p<0.01, n=11).
Our data indicate that global PEDF deficiency intensifies glomerular injury in STZ-induced mouse model of diabetes. An important drawback of most murine models of diabetic kidney disease is the lack of hypertension, a known key factor that accelerates progression to CKD in humans. In contrast, we found that STZ-treated SERPINF1-/- mice become hypertensive. Together, our findings point to SERPINF1-/- mice as an attractive model to study diabetic kidney disease and hypertension in mice and suggest an important causative role of PEDF downregulation in glomerular pathology in diabetes.
Author Disclosures: M. Ye: None. O. Volpert: None. J. Wysocki: None. D. Batlle: None.
- © 2015 by American Heart Association, Inc.