Dataset Information

Ferroptosis in liver disease: new insights into disease mechanisms.

ABSTRACT: Characterized by excessive iron accumulation and lipid peroxidation, ferroptosis is a novel form of iron-dependent cell death, which is morphologically, genetically, and biochemically distinct from other well-known cell death. In recent years, ferroptosis has been quickly gaining attention in the field of liver diseases, as the liver is predisposed to oxidative injury and generally, excessive iron accumulation is a primary characteristic of most major liver diseases. In the current review, we first delineate three cellular defense mechanisms against ferroptosis (GPx4 in the mitochondria and cytosol, FSP1 on plasma membrane, and DHODH in mitochondria), along with four canonical modulators of ferroptosis (system Xc^-, nuclear factor erythroid 2-related factor 2, p53, and GTP cyclohydrolase-1). Next, we review recent progress of ferroptosis studies delineating molecular mechanisms underlying the pathophysiology of several common liver diseases including ischemia/reperfusion-related injury (IRI), nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), hemochromatosis (HH), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). Furthermore, we also highlight both challenges and promises that emerged from recent studies that should be addressed and pursued in future investigations before ferroptosis regulation could be adopted as an effective therapeutic target in clinical practice.

SUBMITTER: Wu J

PROVIDER: S-EPMC8492622 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Liver transplant tissues offer the unique opportunity to model the longitudinal protein abundance changes occurring during hepatitis C virus (HCV)-associated liver disease progression in vivo. In this study, our goal was to identify molecular signatures, and potential key regulatory proteins, representative of the processes influencing early progression to fibrosis. We performed global protein profiling analyses on 24 liver biopsy specimens obtained from 15 HCV(+) liver transplant recipients at 6 and/or 12 months posttransplantation. Differentially regulated proteins associated with early progression to fibrosis were identified by analysis of the area under the receiver operating characteristic curve. Analysis of serum metabolites was performed on samples obtained from an independent cohort of 60 HCV(+) liver transplant patients. Computational modeling approaches were applied to identify potential key regulatory proteins of liver fibrogenesis. Among 4,324 proteins identified, 250 exhibited significant differential regulation in patients with rapidly progressive fibrosis. Patients with rapid fibrosis progression exhibited enrichment in differentially regulated proteins associated with various immune, hepatoprotective, and fibrogenic processes. The observed increase in proinflammatory activity and impairment in antioxidant defenses suggests that patients who develop significant liver injury experience elevated oxidative stresses. This was supported by an independent study demonstrating the altered abundance of oxidative stress-associated serum metabolites in patients who develop severe liver injury. Computational modeling approaches further highlight a potentially important link between HCV-associated oxidative stress and epigenetic regulatory mechanisms impacting on liver fibrogenesis.Our proteome and metabolome analyses provide new insights into the role for increased oxidative stress in the rapid fibrosis progression observed in HCV(+) liver transplant recipients. These findings may prove useful in prognostic applications for predicting early progression to fibrosis.

Dataset Information

Ferroptosis in liver disease: new insights into disease mechanisms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets