Hepatic nerve growth factor induced by iron overload triggers defenestration in liver sinusoidal endothelial cells.
Biochim Biophys Acta
; 1852(1): 175-83, 2015 Jan.
Article
in En
| MEDLINE
| ID: mdl-25460199
ABSTRACT
The fenestrations of liver sinusoidal endothelial cells (LSECs) play important roles in the exchange of macromolecules, solutes, and fluid between blood and surrounding liver tissues in response to hepatotoxic drugs, toxins, and oxidative stress. As excess iron is a hepatotoxin, LSECs may be affected by excess iron. In this study, we found a novel link between LSEC defenestration and hepatic nerve growth factor (NGF) in iron-overloaded mice. By Western blotting, NGF was highly expressed, whereas VEGF and HGF were not, and hepatic NGF mRNA levels were increased according to digital PCR. Immunohistochemically, NGF staining was localized in hepatocytes, while TrkA, an NGF receptor, was localized in LSECs. Scanning electron microscopy revealed LSEC defenestration in mice overloaded with iron as well as mice treated with recombinant NGF. Treatment with conditioned medium from iron-overloaded primary hepatocytes reduced primary LSEC fenestrations, while treatment with an anti-NGF neutralizing antibody or TrkA inhibitor, K252a, reversed this effect. However, iron-loaded medium itself did not reduce fenestration. In conclusion, iron accumulation induces NGF expression in hepatocytes, which in turn leads to LSEC defenestration via TrkA. This novel link between iron and NGF may aid our understanding of the development of chronic liver disease.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Iron Overload
/
Nerve Growth Factor
/
Endothelium
/
Liver
Limits:
Animals
Language:
En
Journal:
Biochim Biophys Acta
Year:
2015
Document type:
Article
Affiliation country:
Japan