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DOI: 10.14670/HH-11-885
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Título: | Treatment with a selective histone deacetylase 6 inhibitor decreases lupus nephritis in NZB/W mice |
Fecha de publicación: | 2017 |
Editorial: | Universidad de Murcia. Departamento de Biología Celular e Histología |
Cita bibliográfica: | Histology and Histopathology, Vol.32, nº12, (2017) |
ISSN: | 1699-5848 0213-3911 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología |
Palabras clave: | Lupus Nephritis Histone deacetylase inhibitor Alpha-tubulin |
Resumen: | To date, there are 18 histone deacetylase (HDAC) enzymes, divided into four classes, which alter protein function by removing acetyl groups from lysine residues. Prior studies report that non-selective HDAC inhibitors decrease disease in lupus mouse models. Concern for adverse side effects of non-selective HDAC inhibition supports investigation of selective-HDAC inhibition. We hypothesized that a selective HDAC-6 inhibitor (HDAC6i) will alleviate disease in a mouse model of lupus by increasing acetylation of alphatubulin. Intraperitoneal injections of the selective HDAC6i ACY-1083 (0.3 mg/kg, 1 mg/kg, or 3 mg/kg), vehicle control, or dexamethasone were administered to 21-week-old, female NZB/W mice, 5 days a week, for 13 weeks. Disease progression was evaluated by proteinuria, serum levels of anti-dsDNA antibody, cytokines and immunoglobulins, and post mortem evaluation of nephritis and T cell populations in the spleen. HDAC6i treatment decreased proteinuria, glomerular histopathology, IgG, and C3 scores when compared to vehicle-treated mice. Within glomeruli of HDAC6i-treated mice, there was increased acetylation of alpha-tubulin and decreased NF-κB. Additionally, HDAC6i decreased serum IL-12/IL-23 and Th17 cells in the spleen. Taken together, these results suggest HDAC6 inhibition may decrease lupus nephritis in NZB/W mice via mechanisms involving acetylation of alphatubulin and decreased NF-κB in glomeruli as well as inhibition of Th17 cells. |
Autor/es principal/es: | Vieson, Miranda D. Gojmerac, Alexander M. Khan, Deena Dai, Rujuan van Duzer, John H. Mazitschek, Ralph Caudell, David L. Liao, Xiaofeng Luo, Xin M. Reilly, Christopher M. |
URI: | http://hdl.handle.net/10201/118008 |
DOI: | DOI: 10.14670/HH-11-885 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 16 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Aparece en las colecciones: | Vol.32,nº12 (2017) |
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Vieson-32-1317-1332-2017.pdf | 11,76 MB | Adobe PDF | Visualizar/Abrir |
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