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Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia.
Olney, Kimberly C; de Ávila, Camila; Todd, Kennedi T; Tallant, Lauren E; Barnett, J Hudson; Gibson, Katelin A; Hota, Piyush; Pandiane, Adithya Shyamala; Durgun, Pinar Cay; Serhan, Michael; Wang, Ran; Lind, Mary Laura; Forzani, Erica; Gades, Naomi M; Thomas, Leslie F; Fryer, John D.
Afiliación
  • Olney KC; Department of Neuroscience, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, USA.
  • de Ávila C; Department of Neuroscience, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, USA.
  • Todd KT; Department of Neuroscience, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, USA.
  • Tallant LE; Department of Neuroscience, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, USA.
  • Barnett JH; Mayo Clinic Graduate School of Biomedical Sciences, Scottsdale, AZ, USA.
  • Gibson KA; Department of Neuroscience, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, USA.
  • Hota P; Mayo Clinic Graduate School of Biomedical Sciences, Scottsdale, AZ, USA.
  • Pandiane AS; MD/PhD Training Program, Mayo Clinic, Scottsdale, AZ, USA.
  • Durgun PC; Department of Neuroscience, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, USA.
  • Serhan M; Division of Nephrology & Hypertension, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, USA.
  • Wang R; School of Engineering of Matter, Transport & Energy, Arizona State University, Tempe, AZ, USA.
  • Lind ML; School of Engineering of Matter, Transport & Energy, Arizona State University, Tempe, AZ, USA.
  • Forzani E; School of Engineering of Matter, Transport & Energy, Arizona State University, Tempe, AZ, USA.
  • Gades NM; School of Engineering of Matter, Transport & Energy, Arizona State University, Tempe, AZ, USA.
  • Thomas LF; School of Engineering of Matter, Transport & Energy, Arizona State University, Tempe, AZ, USA.
  • Fryer JD; School of Engineering of Matter, Transport & Energy, Arizona State University, Tempe, AZ, USA.
J Neuroinflammation ; 21(1): 9, 2024 Jan 04.
Article en En | MEDLINE | ID: mdl-38178237
ABSTRACT
Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Endotoxemia Límite: Animals / Humans Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Endotoxemia Límite: Animals / Humans Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos