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Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0239946 (
liver fibrosis
)
8,268
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Advanced fibrosis and portal hypertension influence short-term mortality.
Lipocalin 2
(
LCN2
) regulates infection response and increases in liver injury. We explored the role of intrahepatic
LCN2
in human alcoholic hepatitis (AH) with advanced fibrosis and portal hypertension and in experimental mouse fibrosis. We found hepatic
LCN2
expression and serum
LCN2
level markedly increased and correlated with disease severity and portal hypertension in patients with AH. In control human livers,
LCN2
expressed exclusively in mononuclear cells, while its expression was markedly induced in AH livers, not only in mononuclear cells but also notably in hepatocytes. Lcn2
-/-
mice were protected from
liver fibrosis
caused by either ethanol or CCl
4
exposure. Microarray analysis revealed downregulation of matrisome, cell cycle and immune related gene sets in Lcn2
-/-
mice exposed to CCl
4
, along with decrease in Timp1 and Edn1 expression. Hepatic expression of COL1A1, TIMP1 and key EDN1 system components were elevated in AH patients and correlated with hepatic
LCN2
expression. In vitro, recombinant
LCN2
induced COL1A1 expression. Overexpression of
LCN2
increased HIF1A that in turn mediated EDN1 upregulation.
LCN2
contributes to
liver fibrosis
and portal hypertension in AH and could represent a new therapeutic target.
...
PMID:Hepatic lipocalin 2 promotes liver fibrosis and portal hypertension. 3296 10
