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Article

Activated Histone Acetyltransferase p300/CBP-Related Signalling Pathways Mediate Up-Regulation of NADPH Oxidase, Inflammation, and Fibrosis in Diabetic Kidney

Institute of Cellular Biology and Pathology, “Nicolae Simionescu” of the Romanian Academy, 050568 Bucharest, Romania
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Author to whom correspondence should be addressed.
Academic Editors: Chiara Nediani and Monica Dinu
Antioxidants 2021, 10(9), 1356; https://doi.org/10.3390/antiox10091356
Received: 21 July 2021 / Revised: 20 August 2021 / Accepted: 21 August 2021 / Published: 26 August 2021
Accumulating evidence implicates the histone acetylation-based epigenetic mechanisms in the pathoetiology of diabetes-associated micro-/macrovascular complications. Diabetic kidney disease (DKD) is a progressive chronic inflammatory microvascular disorder ultimately leading to glomerulosclerosis and kidney failure. We hypothesized that histone acetyltransferase p300/CBP may be involved in mediating diabetes-accelerated renal damage. In this study, we aimed at investigating the potential role of p300/CBP in the up-regulation of renal NADPH oxidase (Nox), reactive oxygen species (ROS) production, inflammation, and fibrosis in diabetic mice. Diabetic C57BL/6J mice were randomized to receive 10 mg/kg C646, a selective p300/CBP inhibitor, or its vehicle for 4 weeks. We found that in the kidney of C646-treated diabetic mice, the level of H3K27ac, an epigenetic mark of active gene expression, was significantly reduced. Pharmacological inhibition of p300/CBP significantly down-regulated the diabetes-induced enhanced expression of Nox subtypes, pro-inflammatory, and pro-fibrotic molecules in the kidney of mice, and the glomerular ROS overproduction. Our study provides evidence that the activation of p300/CBP enhances ROS production, potentially generated by up-regulated Nox, inflammation, and the production of extracellular matrix proteins in the diabetic kidney. The data suggest that p300/CBP-pharmacological inhibitors may be attractive tools to modulate diabetes-associated pathological processes to efficiently reduce the burden of DKD. View Full-Text
Keywords: diabetes; nephropathy; epigenetics; histone acetylation; p300/CBP; NADPH oxidase; oxidative stress diabetes; nephropathy; epigenetics; histone acetylation; p300/CBP; NADPH oxidase; oxidative stress
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MDPI and ACS Style

Lazar, A.-G.; Vlad, M.-L.; Manea, A.; Simionescu, M.; Manea, S.-A. Activated Histone Acetyltransferase p300/CBP-Related Signalling Pathways Mediate Up-Regulation of NADPH Oxidase, Inflammation, and Fibrosis in Diabetic Kidney. Antioxidants 2021, 10, 1356. https://doi.org/10.3390/antiox10091356

AMA Style

Lazar A-G, Vlad M-L, Manea A, Simionescu M, Manea S-A. Activated Histone Acetyltransferase p300/CBP-Related Signalling Pathways Mediate Up-Regulation of NADPH Oxidase, Inflammation, and Fibrosis in Diabetic Kidney. Antioxidants. 2021; 10(9):1356. https://doi.org/10.3390/antiox10091356

Chicago/Turabian Style

Lazar, Alexandra-Gela, Mihaela-Loredana Vlad, Adrian Manea, Maya Simionescu, and Simona-Adriana Manea. 2021. "Activated Histone Acetyltransferase p300/CBP-Related Signalling Pathways Mediate Up-Regulation of NADPH Oxidase, Inflammation, and Fibrosis in Diabetic Kidney" Antioxidants 10, no. 9: 1356. https://doi.org/10.3390/antiox10091356

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