University thesis:
Dissertation, Friedrich-Schiller-Universität Jena, 2022
Footnote:
Kumulative Dissertation, enthält Zeitschriftenaufsätze
Tag der Verteidigung: 06.12.2022
Zusammenfassungen in deutscher und englischer Sprache
Description:
Age is one of the important risk factors to develop malignant diseases leading to a high incidence of liver tumors in the elderly. For aged patients who are eligible for partial hepatectomy, age-related insufficient liver regeneration after partial liver resection may cause postoperative liver failure; For patients with unresectable liver tumors, current systemic treatment regimens are prone to drug resistance and may cause adverse effects. Drug resistance of the rapidly proliferating hepatocellular carcinoma cells (HCCs) may lead to a poorer prognosis for patients. Recent studies have shown that autophagy is closely related to the proliferation of liver cells, but the specific mechanism remains unclear. As reported in manuscript I, we focused on the effects of regulation of autophagy on physiological and pathological processes of the aged liver. Up-regulating autophagy alleviates liver steatosis, ROS-induced cellular stress and augments hepatocyte proliferation. However, upregulating autophagy may aggravate liver fibrosis. As described in manuscript II, the influence of autophagy inhibition on the proliferation of HCCs was investigated. In this study we used HepG2 cells as cell culture model. Blocking autophagy using chloroquine inhibited proliferation of HepG2 cells may by increasing intracellular lipid accumulation and reducing ATP synthesis. As reported in manuscript III, aging may weaken autophagy level through lipofuscin accumulation and inhibition of autophagosome formation. Accumulating evidence have shown that the reduced regenerative capacity of the aged remnant liver could be restored by up-regulating autophagy. Induction of autophagy through the mTOR-independent pathways does not directly affect cell proliferation. Therefore, induction of autophagy by an mTOR-independent autophagy inducer is a promising therapy to facilitate liver regeneration.