AI Article Synopsis
- Senescence is a significant risk factor for liver fibrosis, and Sirtuin 1 (SIRT1) may play a key role in its development, particularly in aged rats exposed to carbon tetrachloride (CCl).
- The study found that SIRT1 levels were decreased in fibrotic liver tissues, leading to increased NLRP3 inflammasome activity and p53/p21 pathway activation, which were associated with inflammation and cell aging.
- Overexpressing SIRT1 through adenoviral vectors was shown to reverse these effects by deacetylating HnRNP U, ultimately reducing liver fibrosis in senescent hepatocytes.
Article Abstract
Senescence represents a major risk factor promoting liver fibrosis progression. Sirtuin 1 (SIRT1), an essential regulator of cellular senescence, may be involved in developing liver fibrosis. However, the role and mechanism of SIRT1 in liver fibrosis development were largely unknown. We constructed the liver fibrosis in aged rats induced by carbon tetrachloride (CCl) and then transfected with GFP-SIRT1 adenoviral vectors. After that, we performed acetylomic analysis of liver tissue in aged rats to identify potential substrates of SIRT1. Furthermore, replicative senescent rat hepatocytes were pretreated with siRNA HnRNP U, SIRT1 adenoviral vectors, resveratrol, and siRNA SIRT1, following stimulation with HO. We found that the protein levels of SIRT1 and HnRNP U were down-regulation in aged rat liver fibrotic tissues, with an accumulation of NLRP3 inflammasome and activation of the p53/p21 pathway in liver tissue, as well as an increased level of plasma IL-1β secretion. In comparison, these effects were reversed by overexpressing SIRT1 with adenoviral vectors. Acetylation of HnRNP U and its sites at K28 and K787 might be potential targets for SIRT1-mediated liver fibrosis in aged rats. Silencing HnRNP U reduced HO-induced up-regulation expression of p53, p21, and NLRP3 inflammasome at protein levels. Additionally, HO induced high acetylation of HnRNP U in senescent hepatocytes, whereas overexpressing SIRT1 with adenoviral vectors and resveratrol deacetylate HnRNP U to inhibit NLRP3 inflammasome and the p53/p21 pathway. Besides, the silence of SIRT1 aggravated HO-induced p53-related senescence and NLRP3-related inflammation in senescent hepatocytes. Our findings suggested that deacetylation of HnRNPU mediated by SIRT1 attenuated liver fibrosis in the elderly by inhibiting p53/p21 pathway and NLRP3-related inflammation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.intimp.2024.113026 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.
Sci Adv
January 2025
Department of Biochemistry, College of Life Science and Biotechnology, Brain Korea 21 Project, Yonsei University, Seoul 03722, Republic of Korea.
Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.
View Article and Find Full Text PDFCHROMOPHOBE HEPATOCELLULAR CARCINOMA: DIAGNOSTIC CHALLENGES.
Arq Bras Cir Dig
January 2025
Mongi Slim Hospital, Department of Pathology - Marsa, Tuni, Tunísia.
Background: Hepatocellular carcinoma (HCC) encompasses rare variants like chromophobe hepatocellular carcinoma (CHCC) characterized by distinct histological features and molecular profiles.
Case Report: A 56-year-old male with chronic hepatitis C, presenting pain in the right hypochondrium. Imaging revealed a solitary liver lesion, subsequently resected and histologically diagnosed as HCC.
Impact of high body mass index on hepatocellular carcinoma risk in chronic liver disease: A population-based prospective cohort study.
PLoS One
January 2025
Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, South Korea.
Background And Aims: We investigated associations between body mass index (BMI) and hepatocellular carcinoma (HCC) in patients with hepatitis B (HBV) C (HCV) virus infection, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and liver cirrhosis (LC).
Methods: We followed 350,608 Korean patients with liver disease who underwent routine health examinations from 2003-2006 until December 2018 via national hospital discharge records. Multivariable adjusted hazard ratios (HRs) per 5-kg/m2 BMI increase (BMI ≥25 kg/m2) for HCC risk were calculated using Cox models.
Cost-effectiveness of monitoring and liver cancer surveillance among patients with inactive chronic hepatitis B.
PLoS One
January 2025
Department of Surgery, Asian Liver Center, Stanford University School of Medicine, Stanford, California, United States of America.
Patients with chronic hepatitis B infection (CHB) have an increased risk for death from liver cirrhosis and hepatocellular carcinoma (HCC). In the United States, only an estimated 37% of adults with chronic hepatitis B diagnosis without cirrhosis receive monitoring with at least an annual alanine transaminase (ALT) and hepatitis B deoxyribonucleic acid (DNA), and an estimated 59% receive antiviral treatment when they develop active hepatitis or cirrhosis. A Markov model was used to calculate the costs, health impact and cost-effectiveness of increased monitoring of adults with HBeAg negative inactive or HBeAg positive immune tolerant CHB who have no cirrhosis or significant fibrosis and are not recommended by the current American Association for the Study of Liver Diseases (AASLD) clinical practice guidelines to receive antiviral treatment, and to assess whether the addition of HCC surveillance would be cost-effective.
View Article and Find Full Text PDFPBCS-ConvNeXt: Convolutional Network-Based Automatic Diagnosis of Non-alcoholic Fatty Liver in Abdominal Ultrasound Images.
J Imaging Inform Med
January 2025
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver condition characterized by excessive hepatic fat accumulation. Early diagnosis is crucial as NAFLD can progress to more severe conditions like steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma without timely intervention. While liver biopsy remains the gold standard for NAFLD assessment, abdominal ultrasound (US) imaging has emerged as a widely adopted non-invasive modality due to convenience and low cost.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!