Activated Protein C Protects Against Diabetic Nephropathy By Inhibiting Endothelial And Podocyte Apoptosis

dc.creatorIsermann B.
dc.creatorVinnikov I.A.
dc.creatorMadhusudhan T.
dc.creatorHerzog S.
dc.creatorKashif M.
dc.creatorBlautzik J.
dc.creatorCorat M.A.F.
dc.creatorZeier M.
dc.creatorBlessing E.
dc.creatorOh J.
dc.creatorGerlitz B.
dc.creatorBerg D.T.
dc.creatorGrinnell B.W.
dc.creatorChavakis T.
dc.creatorEsmon C.T.
dc.creatorWeiler H.
dc.creatorBierhaus A.
dc.creatorNawroth P.P.
dc.date2007
dc.date2015-06-30T18:49:22Z
dc.date2015-11-26T14:36:58Z
dc.date2015-06-30T18:49:22Z
dc.date2015-11-26T14:36:58Z
dc.date.accessioned2018-03-28T21:41:06Z
dc.date.available2018-03-28T21:41:06Z
dc.identifier
dc.identifierNature Medicine. , v. 13, n. 11, p. 1349 - 1358, 2007.
dc.identifier10788956
dc.identifier10.1038/nm1667
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-35948934636&partnerID=40&md5=0f8854fb101ba4871cc073d3b578536c
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/104948
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/104948
dc.identifier2-s2.0-35948934636
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1248957
dc.descriptionData 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. © 2007 Nature Publishing Group.
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dc.descriptionRenal Data System: USRDS 1998 Annual Data Report (NIH Publ. No. 98-3176) (US Government Printing Office, Washington, DC, 1998)Wendt, T.M., RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy (2003) Am. J. Pathol, 162, pp. 1123-1137
dc.descriptionHaraldsson, B., Sorensson, J., Why do we not all have proteinuria? An update of our current understanding of the glomerular barrier (2004) News Physiol. Sci, 19, pp. 7-10
dc.descriptionDalla Vestra, M., Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes (2003) Diabetes, 52, pp. 1031-1035
dc.descriptionMeyer, T.W., Bennett, P.H., Nelson, R.G., Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria (1999) Diabetologia, 42, pp. 1341-1344
dc.descriptionEsmon, C.T. Inflammation and the activated protein C anticoagulant pathway. Semin. Thromb. Hemost. 32 (Suppl. 1), 49-60 (2006)Riewald, M., Petrovan, R.J., Donner, A., Mueller, B.M., Ruf, W., Activation of endothelial cell protease activated receptor 1 by the protein C pathway (2002) Science, 296, pp. 1880-1882
dc.descriptionCheng, T., Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective (2003) Nat. Med, 9, pp. 338-342
dc.descriptionFeistritzer, C., Riewald, M., Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation (2005) Blood, 105, pp. 3178-3184
dc.descriptionFinigan, J.H., Activated protein C mediates novel lung endothelial barrier enhancement: Role of sphingosine 1-phosphate receptor transactivation (2005) J. Biol. Chem, 280, pp. 17286-17293
dc.descriptionBorcea, V., Influence of ramipril on the course of plasma thrombomodulin in patients with diabetes mellitus (1999) Vasa, 28, pp. 172-180
dc.descriptionFujiwara, Y., Tagami, S., Kawakami, Y., Circulating thrombomodulin and hematological alterations in type 2 diabetic patients with retinopathy (1998) J. Atheroscler. Thromb, 5, pp. 21-28
dc.descriptionWeiler-Guettler, H., A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state (1998) J. Clin. Invest, 101, pp. 1983-1991
dc.descriptionHall, S.W., Nagashima, M., Zhao, L., Morser, J., Leung, L.L., Thrombin interacts with thrombomodulin, protein C, and thrombin-activatable fibrinolysis inhibitor via specific and distinct domains (1999) J. Biol. Chem, 274, pp. 25510-25516
dc.descriptionFesta, A., Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study (2000) Kidney Int, 58, pp. 1703-1710
dc.descriptionIsermann, B., The thrombomodulin-protein C system is essential for the maintenance of pregnancy (2003) Nat. Med, 9, pp. 331-337
dc.descriptionMosnier, L.O., Griffin, J.H., Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease-activated receptor-1 and endothelial cell protein C receptor (2003) Biochem. J, 373, pp. 65-70
dc.descriptionTewari, M., Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase (1995) Cell, 81, pp. 801-809
dc.descriptionWang, J., Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria (2004) J. Biol. Chem, 279, pp. 19948-19954
dc.descriptionKelly, K.J., Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury (2004) Am. J. Physiol. Renal Physiol, 287, pp. F760-F766
dc.descriptionBrownlee, M., Biochemistry and molecular cell biology of diabetic complications (2001) Nature, 414, pp. 813-820
dc.descriptionZou, M.H., Shi, C., Cohen, R.A., High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H(2) receptor-mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cells (2002) Diabetes, 51, pp. 198-203
dc.descriptionYamaji, K., Activated protein C, a natural anticoagulant protein, has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation (2005) Thromb. Res, 115, pp. 319-325
dc.descriptionRiewald, M., Ruf, W., Protease-activated receptor-1 signaling by activated protein C in cytokine-perturbed endothelial cells is distinct from thrombin signaling (2005) J. Biol. Chem, 280, pp. 19808-19814
dc.descriptionGoligorsky, M.S., Chen, J., Brodsky, S., Workshop: Endothelial cell dysfunction leading to diabetic nephropathy: focus on nitric oxide (2001) Hypertension, 37, pp. 744-748
dc.descriptionEndemann, D.H., Schiffrin, E.L., Endothelial dysfunction (2004) J. Am. Soc. Nephrol, 15, pp. 1983-1992
dc.descriptionMurata, I., Apoptotic cell loss following cell proliferation in renal glomeruli of Otsuka Long-Evans Tokushima Fatty rats, a model of human type 2 diabetes (2002) Am. J. Nephrol, 22, pp. 587-595
dc.descriptionKumar, D., Robertson, S., Burns, K.D., Evidence of apoptosis in human diabetic kidney (2004) Mol. Cell. Biochem, 259, pp. 67-70
dc.descriptionBaba, K., Involvement of apoptosis in patients with diabetic nephropathy: A study on plasma soluble Fas levels and pathological findings (2004) Nephrology (Carlton), 9, pp. 94-99
dc.descriptionLiaw, P.C., Patients with severe sepsis vary markedly in their ability to generate activated protein C (2004) Blood, 104, pp. 3958-3964
dc.descriptionMacias, W.L., New insights into the protein C pathway: Potential implications for the biological activities of drotrecogin alfa (activated) (2005) Crit. Care, 9 (SUPPL. 4), pp. S38-S45
dc.descriptionGlaser, C.B., Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. A potential rapid mechanism for modulation of coagulation (1992) J. Clin. Invest, 90, pp. 2565-2573
dc.descriptionBoehme, M.W., Release of thrombomodulin from endothelial cells by concerted action of TNF-alpha and neutrophils: In vivo and in vitro studies (1996) Immunology, 87, pp. 134-140
dc.descriptionMosnier, L.O., Gale, A.J., Yegneswaran, S., Griffin, J.H., Activated protein C variants with normal cytoprotective but reduced anticoagulant activity (2004) Blood, 104, pp. 1740-1744
dc.descriptionBernard, G.R., Safety assessment of drotrecogin alfa (activated) in the treatment of adult patients with severe sepsis (2003) Crit. Care, 7, pp. 155-163
dc.descriptionTaylor, F.B., Kinasewitz, G., Activated protein C in sepsis (2004) J. Thromb. Haemost, 2, pp. 708-717
dc.descriptionChae, S.S., Proia, R.L., Hla, T., Constitutive expression of the S1P1 receptor in adult tissues (2004) Prostaglandins Other Lipid Mediat, 73, pp. 141-150
dc.descriptionVirag, L., Szabo, C., The therapeutic potential of poly(ADP-ribose) polymerase inhibitors (2002) Pharmacol. Rev, 54, pp. 375-429
dc.descriptionCipriani, G., Nuclear poly(ADP-ribose) polymerase-1 rapidly triggers mitochondrial dysfunction (2005) J. Biol. Chem, 280, pp. 17227-17234
dc.descriptionAlano, C.C., Kauppinen, T.M., Valls, A.V., Swanson, R.A., Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 9685-9690
dc.descriptionSzabo, C., Biser, A., Benko, R., Bottinger, E., Susztak, K., Poly(ADP-ribose) polymerase inhibitors ameliorate nephropathy of type 2 diabetic Leprdb/db mice (2006) Diabetes, 55, pp. 3004-3012
dc.descriptionKiss, L., The pathogenesis of diabetic complications: The role of DNA injury and poly(ADP-ribose) polymerase activation in peroxynitrite-mediated cytotoxicity (2005) Mem. Inst. Oswaldo Cruz, 100 (SUPPL. 1), pp. 29-37
dc.descriptionRichardson, M.A., Gerlitz, B., Grinnell, B.W., Enhancing protein C interaction with thrombin results in a clot-activated anticoagulant (1992) Nature, 360, pp. 261-264
dc.descriptionChen, M., Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease (2000) Nat. Med, 6, pp. 797-801
dc.descriptionIsermann, B., Endothelium-specific loss of murine thrombomodulin disrupts the protein C anticoagulant pathway and causes juvenile-onset thrombosis (2001) J. Clin. Invest, 108, pp. 537-546
dc.descriptionKerlin, B.A., Survival advantage associated with heterozygous Factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia (2003) Blood, 102, pp. 3085-3092
dc.descriptionCalkin, A.C., PPAR-α and -γ agonists attenuate diabetic kidney disease in the apolipoprotein E knockout mouse (2006) Nephrol. Dial. Transplant, 21, pp. 2399-2405
dc.descriptionMundel, P., Rearrangements of the cytoskeleton and cell contacts induce process formation during differentiation of conditionally immortalized mouse podocyte cell lines (1997) Exp. Cell Res, 236, pp. 248-258
dc.descriptionAsanuma, K., Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner (2005) J. Clin. Invest, 115, pp. 1188-1198
dc.languageen
dc.publisher
dc.relationNature Medicine
dc.rightsfechado
dc.sourceScopus
dc.titleActivated Protein C Protects Against Diabetic Nephropathy By Inhibiting Endothelial And Podocyte Apoptosis
dc.typeArtículos de revistas


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