Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations

Liver fibrosis results from many chronic injuries and may often progress to cirrhosis hepatocellular carcinoma (HCC). In fact, up 90% of HCC arise in a cirrhotic liver. Conversely, stress is implicated liver damage, worsening disease outcome. Hence, could play role disrupting homeostasis, concept that has not been fully explored. Here, murine model TAA-induced we identified nerve growth factor (NGF) be crucial regulator the stress-induced fibrogenesis signaling pathway as it activates its receptor p75 neurotrophin (p75NTR), increasing damage. Additionally, blocking NGF decreased whereas treatment with recombinant accelerated fibrotic process similar extent than challenge. We further show induced by characterized specific changes hepatoglycocode (increased β1,6GlcNAc-branched complex N-glycans core 1 O-glycans expression) which are also observed patients advanced compared low level fibrosis. Our study facilitates an understanding injury identify early stages disease, contributes established fibrogenesis.