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• W1488403741 abstract "Necrotic lesions and necrotic cell death characterize severe autoimmune nephritides, and contribute to local inflammation and to progression of the disease. Poly(ADP-ribose) polymerase-1 (PARP-1), a DNA repair enzyme, is involved in the induction of necrosis and is a key player in the acute and chronic inflammation. Therefore, we hypothesized that PARP-1 controls the severity of nephritis by mediating the induction of necrosis in the kidney. We used lupus and anti-glomerular basement membrane models of nephritis to determine the effects of PARP-1 on the inflammatory response in the kidney. We show in this study that PARP-1 is indeed activated during the course of glomerulonephritis. We also show that the absence of PARP-1 or its pharmacological inhibition results in milder nephritis, with lower blood urea nitrogen levels, reduced necrotic lesions, and higher survival rates. The relevance of PARP-1 showed a strong male sex specificity, and treatment of male mice with 17beta-estradiol prolonged their survival during the course of nephritis. PARP-1 also regulated TNF-alpha expression and up-regulation of adhesion molecules, further supporting a role of PARP-1 in the inflammatory process within the kidney. Our results demonstrate that PARP-1 activation and consequent necrotic cell death play an important role in the pathogenesis of male nephritis, and suggest that PARP-1 can be a novel therapeutic target in glomerulonephritis." @default.
• W1488403741 created "2016-06-24" @default.
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• W1488403741 date "2009-06-01" @default.
• W1488403741 modified "2023-09-23" @default.
• W1488403741 title "Poly(ADP-Ribose) Polymerase-1 Regulates the Progression of Autoimmune Nephritis in Males by Inducing Necrotic Cell Death and Modulating Inflammation" @default.
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• W1488403741 doi "https://doi.org/10.4049/jimmunol.0803565" @default.
• W1488403741 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4827346" @default.
• W1488403741 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19454727" @default.
• W1488403741 hasPublicationYear "2009" @default.
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