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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis.
J. Nat. Med. 13, 1349-1358 (2007)
Data providing direct evidence for a causative link between endothelial dysfunction, microvascular disease and diabetic end-organ damage are scarce. Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally linked to nephropathy. Thrombomodulin-dependent APC formation mediates cytoprotection in diabetic nephropathy by inhibiting glomerular apoptosis. APC prevents glucose-induced apoptosis in endothelial cells and podocytes, the cellular components of the glomerular filtration barrier. APC modulates the mitochondrial apoptosis pathway via the protease-activated receptor PAR-1 and the endothelial protein C receptor EPCR in glucose-stressed cells. These experiments establish a new pathway, in which hyperglycemia impairs endothelial thrombomodulin-dependent APC formation. Loss of thrombomodulin-dependent APC formation interrupts cross-talk between the vascular compartment and podocytes, causing glomerular apoptosis and diabetic nephropathy. Conversely, maintaining high APC levels during long-term diabetes protects against diabetic nephropathy.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
ISSN (print) / ISBN
1340-3443
e-ISSN
1861-0293
Zeitschrift
Journal of natural medicines
Quellenangaben
Band: 13,
Heft: 11,
Seiten: 1349-1358
Verlag
Springer
Verlagsort
Tokyo [u.a.]
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)