SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response

We have previously demonstrated that the therapeutic inhibition of SPARC or SPARC gene deletion protected mice against liver injury

Estanislao Peixoto; Catalina Atorrasagasti; Mariana Malvicini; Esteban Fiore; Marcelo Rodriguez; Mariana Garcia; Paola Finocchieto; Juan J. Poderoso; Fernando Corrales; Guillermo Mazzolini

2016

Scholarcy highlights

  • Acute and chronic liver damage is a growing worldwide health problem due to the increasing incidence of toxic insults such as alcohol abuse, drugs or metabolic syndrome
  • SPARC−/− mice were protected from acute liver failure induced by concanavalin A and the agonistic anti-CD95 antibody Jo2
  • We further explored the mechanistic role of SPARC in acute and chronic liver pathologies
  • We have shown that SPARC−/− livers exhibits decreased oxidative stress response, and higher proliferative response, which may explain at least in part the hepatic protection from injury
  • The mechanisms by which SPARC inhibits proliferation were related with alteration of growth factors signaling events by diverse mechanisms including interaction with platelet derived growth factor receptors, cyclin E-Cyclin dependent kinase inactivation, cyclin A downregulation, and maintenance of retinoblastoma activation
  • We demonstrated that down-regulation of SPARC on HepG2 cells has no effect on tumor growth in vivo
  • Considering that TAA has the capacity to induce hepatocyte necrosis, apoptosis, reactive oxygen species, and reactive metabolites such as thioacetamide-Soxide, the high catalase activity observed in SPARC null mice might explain the observed protective effects against ROS induction by TAA

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