ArticleThe Journal of pharmacology and experimental therapeutics2012
Hypoxia-inducible factor activation in myeloid cells contributes to the development of liver fibrosis in cholestatic mice.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- Understanding the role of hypoxia inducible factors in liver fibrosis and future therapeutic applications.iLIVER · 2026Review
- Hypoxia in MASLD: a spatial determinant of the pathogenesis.Trends in molecular medicine · 2026Review
- Icaritin Attenuates HSC Activation by Down-regulating the HIF-1α and TGF-β/Smad Signaling Pathways to Ameliorate Liver Fibrosis.Current medicinal chemistry · 2026Article
- The Cardiohepatic Axis in Heart Failure.JACC. Basic to translational science · 2025Review
- Hypoxia-Induced Signaling in Gut and Liver Pathobiology.Annual review of pathology · 2024Review
- Hepatocyte-specific knockout of HIF-2α cannot alleviate carbon tetrachloride-induced liver fibrosis in mice.PeerJ · 2023Article
- Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease.The FEBS journal · 2022Review
- Review
- Targeting SYK of monocyte-derived macrophages regulates liver fibrosis via crosstalking with Erk/Hif1α and remodeling liver inflammatory environment.Cell death & disease · 2021Article
- Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches.Chinese medicine · 2021Article
- Review
- Role of the ROS-JNK Signaling Pathway in Hypoxia-Induced Atrial Fibrotic Responses in HL-1 Cardiomyocytes.International journal of molecular sciences · 2021Article
- Hypoxia-Inducible Factors as Key Players in the Pathogenesis of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis.Frontiers in medicine · 2021Review
- Immune and Metabolic Alterations in Liver Fibrosis: A Disruption of Oxygen Homeostasis?Frontiers in molecular biosciences · 2021Review
- Altered aryl-hydrocarbon-receptor signalling affects regulatory and effector cell immunity in autoimmune hepatitis.Journal of hepatology · 2021Article
- Hypoxia-inducible factors and innate immunity in liver cancer.The Journal of clinical investigation · 2020Review
- Activation of TWIST Transcription by Chromatin Remodeling Protein BRG1 Contributes to Liver Fibrosis in Mice.Frontiers in cell and developmental biology · 2020Article
- Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice.International journal of molecular sciences · 2019Article
- Hypoxia signaling in human diseases and therapeutic targets.Experimental & molecular medicine · 2019Review
- Liver Zonation in Health and Disease: Hypoxia and Hypoxia-Inducible Transcription Factors as Concert Masters.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophages play an integral role in the development of liver fibrosis by releasing mediators, such as platelet-derived growth factor-B (PDGF-B) and transforming growth factor-β1, which stimulate hepatic stellate cell proliferation, chemotaxis, and collagen production. However, the mechanism by which chronic liver injury stimulates macrophages to release these mediators is not completely understood. We tested the hypothesis that chronic liver injury activates hypoxia-inducible factor (HIF) transcription factors in macrophages that regulate the production of mediators that promote fibrosis. To test this hypothesis, Cre/lox technology was used to generate myeloid cell-specific HIF-1α or HIF-1β knockout mice. When these mice were subjected to bile duct ligation (BDL), levels of α-smooth muscle actin and type I collagen in the liver were reduced compared with those of mice with normal levels of HIFs. The deficiency of HIFs in macrophages did not affect liver injury or inflammation after BDL but reduced PDGF-B mRNA and protein, suggesting that HIF activation in macrophages may promote fibrosis by regulating the production of PDGF-B. Consistent with a role for HIFs in liver fibrosis in cholestatic liver disease, nuclear HIF-1α protein was present in macrophages, hepatocytes, and fibroblasts in the livers from patients with primary biliary cirrhosis and primary sclerosing cholangitis. These studies demonstrate that HIFs are important regulators of profibrotic mediator production by macrophages during the development of liver fibrosis and suggest that HIFs may be a novel therapeutic target for the treatment of chronic liver disease in patients.
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Registered trials
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