| First Author | Garsen M | Year | 2016 |
| Journal | Kidney Int | Volume | 90 |
| Issue | 5 | Pages | 1012-1022 |
| PubMed ID | 27575559 | Mgi Jnum | J:317087 |
| Mgi Id | MGI:6844231 | Doi | 10.1016/j.kint.2016.06.035 |
| Citation | Garsen M, et al. (2016) Cathepsin L is crucial for the development of early experimental diabetic nephropathy. Kidney Int 90(5):1012-1022 |
| abstractText | Proteinuria is one of the first clinical signs of diabetic nephropathy and an independent predictor for the progression to renal failure. Cathepsin L, a lysosomal cysteine protease, can be involved in the development of proteinuria by degradation of proteins that are important for normal podocyte architecture, such as the CD2-associated protein, synaptopodin, and dynamin. Cathepsin L also activates heparanase, a heparan sulfate endoglycosidase previously shown to be crucial for the development of diabetic nephropathy. Here, we evaluated the exact mode of action of cathepsin L in the development of proteinuria in streptozotocin-induced diabetes. Cathepsin L-deficient mice, in contrast to their wild-type littermates, failed to develop albuminuria, mesangial matrix expansion, tubulointerstitial fibrosis, and renal macrophage influx and showed a normal renal function. In wild-type mice the early development of albuminuria correlated with the activation of heparanase and loss of heparan sulfate expression, whereas loss of synaptopodin expression and podocyte damage occurred at a later stage. Thus, cathepsin L is causally involved in the pathogenesis of experimental diabetic nephropathy. Most likely, cathepsin L-dependent heparanase activation is crucial for the development of albuminuria and renal damage. |
