2024-03-29T00:17:27Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/136212021-10-27T12:01:39Zcom_10261_109com_10261_1com_10261_22col_10261_362col_10261_275
Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
Mayoral, Rafael
Mollá, Belén
Flores, Juana María
Boscá, Lisardo
Casado, Marta
Martín-Sanz, Paloma
Prostaglandins
Lipopolysaccharide
Concanavalin A
Inflammation
Apoptosis
10 pages, 8 figures.-- PMID: 18671671 [PubMed].-- El pdf del artículo es la versión post-print.
The effect of COX-2-dependent prostaglandins (PGs) in acute liver injury has been investigated in transgenic mice that express human COX-2 in hepatocytes. We have used three well established models of liver injury: Lipopolysaccharide injury in
D-galactosamine preconditioned mice (LPS/D-GalN), the hepatitis induced by
concanavalin A (ConA) and the proliferation of hepatocytes in regenerating liver after
partial hepatectomy (PH). Our data demonstrate that PGs synthesis decreases in
hepatocytes the susceptibility to LPS/D-GalN or ConA-induced liver injury as deduced
by significant lower levels of the pro-inflammatory profile and plasmatic
aminotransferases in transgenic mice, an effect suppressed by COX-2 selective
inhibitors. These transgenic animals express higher levels of anti-apoptotic proteins and exhibit activation of proteins implicated in cell survival, such as Akt and AMP-kinase after injury. The resistance to LPS/D-GalN induced liver apoptosis involves an impairment of procaspase 3 and 8 activation. Protection against ConA-induced injury implies a significant reduction in necrosis. Moreover, hepatocyte commitment to start replication is anticipated in Tg mice after PH, due to the expression of PCNA, cyclin D1 and E. These results show, in a genetic model, that tissue-specific COX-2 dependent PGs exert an efficient protection against acute liver injury by an antiapoptotic/antinecrotic effect and by accelerated early hepatocyte proliferation.
This work was supported by grants SAF2007-60551, SAF2005-1758 and S-BIO-0283/2006. B. M. was supported by grant of FIS-RECAVA RD06/0014/0025. Ciberehd is funded by the Instituto de Salud Carlos III.
Peer reviewed
2009-06-12T11:04:54Z
2009-06-12T11:04:54Z
2008-08-15
artículo
http://purl.org/coar/resource_type/c_6501
Biochemical Journal 416(3): 337-346 (2008)
0264-6021
http://hdl.handle.net/10261/13621
10.1042/BJ20081224
en
Postprint
http://dx.doi.org/10.1042/BJ20081224
open
863943 bytes
application/pdf
Portland Press
Biochemical Society