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Notch1 and Notch2 in podocytes play differential roles during diabetic nephropathy development.
Diabetes 64, 4099-4111 (2015)
Notch pathway activation in podocytes has been shown to play an important role in diabetic kidney disease (DKD) development, however, the receptors and ligands involved in the process have not been identified. Here we report that conditional deletion of Notch1 in podocytes using NPHS2(cre)Notch1(flox/flox) animals resulted in marked amelioration of diabetic kidney disease. On the contrary, podocyte-specific genetic deletion of Notch2 had no effect on albuminuria and mesangial expansion. Notch1-null podocytes were protected from apoptosis and dedifferentiation in vitro, likely explaining the protective phenotype in vivo. Deletion of Notch1 in podocytes also resulted in an increase in Notch2 expression, indicating an interaction between the receptors. At the same time, transgenic overexpression of Notch2 in podocytes did not induce phenotypic changes, while constitutive expression of Notch1 caused rapid development of albuminuria and glomerulosclerosis. In summary, our studies indicate that Notch1 plays a distinct (non-redundant) role in podocytes during diabetic kidney disease development.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
Journal
Diabetes
Quellenangaben
Volume: 64,
Issue: 12,
Pages: 4099-4111
Publisher
American Diabetes Association
Publishing Place
Alexandria, VA.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)