Elevated circulating TGFβ1 during acute liver failure activates TGFβR2 on cortical neurons and exacerbates neuroinflammation and hepatic encephalopathy in mice

• Published in: Journal of neuroinflammation Vol. 16; no. 1; p. 69
• Main Authors: McMillin, Matthew, Grant, Stephanie, Frampton, Gabriel, Petrescu, Anca D, Williams, Elaina, Jefferson, Brandi, Thomas, Alison, Brahmaroutu, Ankita, DeMorrow, Sharon
• Format: Journal Article
• Language: English
• Published: England BioMed Central 02.04.2019; BMC
• Subjects: Acute liver failure; Animals; Antibodies - therapeutic use; Apoptosis; Ataxia; Azoxymethane; Azoxymethane - toxicity; Benzamides - pharmacology; Carcinogens - toxicity; Cell Line, Transformed; Cerebral Cortex - pathology; Chemokines; Coma; Cytokines; Disease Models, Animal; Drug overdose; Encephalopathy; Growth factors; Hepatic encephalopathy; Hepatic Encephalopathy - drug therapy; Hepatic Encephalopathy - etiology; Hydration; Inflammation; Inflammation - drug therapy; Inflammation - etiology; Injection; Interleukin 1; Isoquinolines - pharmacology; Laboratories; Ligands; Liver; Liver - metabolism; Liver - pathology; Liver cancer; Liver failure; Liver Failure, Acute - chemically induced; Liver Failure, Acute - complications; Liver Failure, Acute - genetics; Liver Failure, Acute - pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Microglia - drug effects; Monocyte chemoattractant protein 1; Mortality; Necrosis; Neuroinflammation; Neurological complications; Neurological diseases; Neurons - drug effects; Neurons - metabolism; Phagocytosis; Phagocytosis - drug effects; Phagocytosis - genetics; Pyrazoles - pharmacology; Pyridines - pharmacology; Pyrroles - pharmacology; Receptor, Transforming Growth Factor-beta Type II - deficiency; Receptor, Transforming Growth Factor-beta Type II - genetics; Signal transduction; Signal Transduction - drug effects; Stem cells; Transforming Growth Factor beta1 - blood; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - immunology; Transforming growth factor-b1; Tumor necrosis factor-α; Up-Regulation - drug effects; Up-Regulation - genetics; Acute liver failure; Neuroinflammation; Azoxymethane; Microglia; Necrosis

Acute liver failure resulting from drug-induced liver injury can lead to the development of neurological complications called hepatic encephalopathy (HE). Hepatic transforming growth factor beta 1 (TGFβ1) is upregulated due to liver failure in mice and inhibiting circulating TGFβ reduced HE progress...