title: A novel therapy of inducing hepatocyte hypertrophy by activating Akt/mTORC1 pathway in acute liver failure.
abstract: As a severe clinical syndrome, acute liver failure (ALF) is associated with high morbidity and mortality and liver transplantation is the best treatment of choice in most critically-ill cases, which yet suffers from obvious drawbacks including lack of resources and unnecessary surgery for those who can recover spontaneously. In ALF, massive cell deaths occur whereas liver regeneration via hepatocyte proliferation is largely inhibited. The serine/threonine kinase Akt serves as a central role in regulating signaling of growth factors, cytokines and other cellular stimuli within cell and thus correlates with diverse cellular functions, including the pro-survival pathway by inducing hypertrophy. Physiologically, cellular hypertrophy is an adaption in response to increased functional demand or other stresses. It has been demonstrated recently that Akt/mTORC1-controlled switch of hyperplasia to hypertrophy in pregnancy restored the regenerative capacity of aged liver and pharmacological activation of this pathway is sufficient to induce cell growth in the liver of nonpregnant aged mice. We hypothesized, therefore, that pharmacological therapy targeting to induce hepatocyte hypertrophy by activating the Akt/mTORC1 pathway might be a novel and promising option in the early management of patients with ALF as an alternative way to impaired process of cell proliferation.
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Tao
authors: T
authors: Wei
authors: Ling
authors: L
authors: Yu
authors: Yi
authors: Y
authors: Lv
mesh_terms: D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D017114:Liver Failure, Acute / Q000188:drug therapy*; D008115:Liver Regeneration / Q000187:drug effects*; D000076222:Mechanistic Target of Rapamycin Complex 1; D008954:Models, Biological; D046912:Multiprotein Complexes; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase