ArticleScientific reports2017
Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma.World journal of hepatology · 2024Article
- Hepatic Amyloid Beta-42-Metabolizing Proteins in Liver Steatosis and Metabolic Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2024Article
- Comprehensive scRNA-seq Analysis and Identification of CD8_+T Cell Related Gene Markers for Predicting Prognosis and Drug Resistance of Hepatocellular Carcinoma.Current medicinal chemistry · 2024Article
- Alterations in the hepatocyte epigenetic landscape in steatosis.Epigenetics & chromatin · 2023Article
- Macrophage Nrf2, an anti-inflammatory signal in hepatic ischemia/reperfusion injury.Cellular & molecular immunology · 2023Article
- Per- and polyfluoroalkyl substances activate UPR pathway, induce steatosis and fibrosis in liver cells.Environmental toxicology · 2023Article
- TIMP3 involvement and potentiality in the diagnosis, prognosis and treatment of diabetic nephropathy.Acta diabetologica · 2021Review
- Modulatory effect of euxanthone in liver cancer-bearing obese mice: crosstalk between PPARγ and TIMP3 signalling axes.3 Biotech · 2021Article
- Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy.Nature communications · 2021Article
- Epigenomic and Metabolomic Integration Reveals Dynamic Metabolic Regulation in Bladder Cancer.Cancers · 2021Review
- Continual proteomic divergence of HepG2 cells as a consequence of long-term spheroid culture.Scientific reports · 2021Article
- Strategies to Target ADAM17 in Disease: From its Discovery to the iRhom Revolution.Molecules (Basel, Switzerland) · 2021Review
- Restoration of renal TIMP3 levels via genetics and pharmacological approach prevents experimental diabetic nephropathy.Clinical and translational medicine · 2021Article
- ADAM Metalloproteinase Domain 17 Regulates Cholestasis-Associated Liver Injury and Sickness Behavior Development in Mice.Frontiers in immunology · 2021Article
- SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis.Respiratory research · 2020Article
- Curcumin Inhibits Hepatocellular Carcinoma via Regulating miR-21/TIMP3 Axis.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway.Frontiers in immunology · 2020Article
- Cyclophilin Inhibitor NV556 Reduces Fibrosis and Hepatocellular Carcinoma Development in Mice With Non-Alcoholic Steatohepatitis.Frontiers in pharmacology · 2019Article
- Targeting hepatic miR-221/222 for therapeutic intervention of nonalcoholic steatohepatitis in mice.EBioMedicine · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to hepatocarcinoma. Tissue inhibitor of metalloproteinase 3 (Timp3) has a role in the pathogenesis of fatty liver disease associated with obesity and is silenced during metabolic disorders and liver cancer. We generated an hepatocyte-specific TIMP3 'gain-of-function' mouse model under the control of the Albumin promoter (AlbT3) and investigated its effects during high-fat diet (HFD). After 16 weeks of HFD, TIMP3 overexpression significantly improved glucose metabolism, hepatic fatty acid oxidation and cholesterol homeostasis. In AlbT3 mice CYP7A1, MDR3 and MRP2 gene expressions were observed, consistent with higher bile acid synthesis and export. Next, to evaluate the role of A Disintegrin and Metalloproteinase 17 (ADAM17), a crucial target of TIMP3, in these processes, we created mice deficient in Adam17 specifically in hepatocyte (A17LKO) or in myeloid lineage (A17MKO), founding that only A17LKO showed improvement in liver steatosis induced by HFD. Moreover, both, AlbT3 and A17LKO significantly reduced diethylnitrosamine-initiated, HFD-promoted hepatic tumorigenesis assessed by tumor multiplicity and total tumor area. Taken together, these data indicate that hepatic TIMP3 can slow progression of NAFLD, and tumorigenesis, at least in part, through the regulation of ADAM17 activity.
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