Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/175689
Hepatic lipocalin 2 promotes liver fibrosis and portal hypertension
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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 CCl4 exposure. Microarray analysis revealed downregulation of matrisome, cell cycle and immune related gene sets in Lcn2-/- mice exposed to CCl4, 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.
Matèries
Matèries (anglès)
Citació
Citació
CHEN, Jiegen, ARGEMI, Josep maria, ODENA, Gemma, XU, Ming-jiang, CAI, Yan, MASSEY, Veronica, PARRISH, Austin, VADIGEPALLI, Rajanikanth, ALTAMIRANO, José, CABEZAS, Joaquin, GINÈS I GIBERT, Pere, CABALLERIA ROVIRA, Joan, SNIDER, Natasha, SANCHO BRU, Pau, AKIRA, Shizuo, RUSYN, Ivan, GAO, Bin, BATALLER ALBEROLA, Ramón. Hepatic lipocalin 2 promotes liver fibrosis and portal hypertension. _Scientific Reports_. 2020. Vol. 10, núm. 1, pàgs. 15558. [consulta: 25 de febrer de 2026]. ISSN: 2045-2322. [Disponible a: https://hdl.handle.net/2445/175689]