Blocking nerve growth factor binding to the p75 neurotrophin receptor on sympathetic neurons transiently reduces trkA activation but does not affect neuronal survival

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

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Growth arrest of PC12 cells by nerve growth factor is dependent on the phosphatidylinositol 3-kinase/Akt pathway via p75 neurotrophin receptor

Journal of Neuroscience Research ◽

10.1002/jnr.10564 ◽

2003 ◽

Vol 72 (2) ◽

pp. 211-217 ◽

Cited By ~ 13

Author(s):

Hisanori Ito ◽

Hiroshi Nomoto ◽

Shoei Furukawa

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Pc12 Cells ◽

Growth Arrest ◽

Neurotrophin Receptor ◽

Akt Pathway ◽

P75 Neurotrophin Receptor ◽

Phosphatidylinositol 3 Kinase ◽

Nerve Growth ◽

Phosphatidylinositol 3

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Role of nerve growth factor in the development of rat sympathetic neurons in vitro. III. Effect on acetylcholine production.

The Journal of Cell Biology ◽

10.1083/jcb.75.3.712 ◽

1977 ◽

Vol 75 (3) ◽

pp. 712-718 ◽

Cited By ~ 48

Author(s):

L L Chun ◽

P H Patterson

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Rat Heart ◽

Neuronal Survival ◽

Sympathetic Neurons ◽

Cell Monolayer ◽

Heart Cell ◽

Heart Cells ◽

Nerve Growth ◽

Rat Heart Cells

The effect of nerve growth factor (NGF) on the development of cholinergic sympathetic neurons was studied in cultures grown either on monolayers of dissociated rat heart cells or in medium conditioned by them. In the presence of rat heart cells the absolute requirement of neurons for exogenous NGF was partially spared. The ability of heart cells to support neuronal survival was due at least in part to production of a diffusable NGF-like substance into the medium. Although some neurons survived on the heart cell monolayer without added NGF, increased levels of exogenous NGF increased neuronal survival until saturation was achieved at 0.5 microgram/ml 7S NGF. The ability of neurons to produce acetylcholine (ACh) from choline was also dependent on the level of exogenous NGF. In mixed neuron-heart cell cultures, NGF increased both ACh and catecholamine (CA) production per neuron to the same extent; saturation occurred at 1 microgram/ml 7S NGF. As cholinergic neurons developed in culture, they became less dependent on NGF for survival and ACh production, but even in older cultures approximately 40% of the neurons died when NGF was withdrawn. Thus, NGF is as necessary for survival, growth, and differentiation of sympathetic neurons when the neurons express cholinergic functions as when the neurons express adrenergic functions (4, 5).

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