Expression of Notch Pathway Protein in Healthy and Diseased Renal Biopsies
First Prize in the Basic Science Group, New York Society of Nephrology Meeting, May 20, 2009
Mariana, Murea, Junki Park, Hideki Kato, Thiruvur Niranjan, Han Si, David Thomas, James Pullman, Michal Melamed and Katalin Susztak
Medicine/Nephrology, Albert Einstein College of Medicine, Bronx, NY, United States; Pathology, Montefiore Medical Center, Bronx, NY
Background: Recent studies suggested that the Notchsignaling pathway is activated in diabetic kidney disease and focal segmental glomeruosclerosis of humans and animal models of thereof. In addition,inhibitors of the pathway ameliorated proteinuria in animal models of renal disease. However, the expression of Notch ligands and receptors is not known inhealthy and diseased human kidneys.
Methods: In this study, we analyzed Notch ligands and receptors expression abundance using fluorescent immunohistochemistry in control and a set of acuired renal diseases in humans,collected baseline demographic, clinical and histopathologic parameters, and examined their correlations with proteinuria, histological changes and renal function.
Results: We found that activeNotch 1 and 2 is expressed in podocytes in different glomerular diseases associated with proteinuria, and not only in diabetic kidney disease and focal segmental glomerulosclerosis. Glomerulosclerosis severity correlated with podocyte and tubular expression of active Notch 1. Tubulointerstitial fibrosis severity correlated with tubular expression of Notch 1. There was a strong correlation between podocyte Notch ligand Jagged 1, tubular active Notch 1,tubular active Notch 2 expression and the renal function.
Conclusion: Notch pathway is commonly activated in a host of acquired renal diseases associated with proteinuria. Ligand and receptor components of this pathway hold differential prognostic (and therefore probably pathomecanistic) implications, since activation of podocyte and tubular Notch 1 receptor (but not Notch 2 receptor) strongly correlates with histologic markers of adverse renal function outcome,and overactivation of Notch ligand Jagged 1 (but not ligand Delta 1) correlateswith decreased renal function.