ArticleHepatology (Baltimore, Md.)2021
Hexa Histidine-Tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species.
Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Therapeutic Potential of Cytoglobin and Neuroglobin in Oxidative Stress-Driven Liver Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Cytoglobin in Hepatic Stellate Cells Plays Anti-Fibrotic Role in Chronic Liver Injury.Antioxidants (Basel, Switzerland) · 2026Review
- Targeting SPP1-CD44-Hedgehog Axis Elicits Therapeutic Effects in Hepatocellular Carcinoma by Suppressing Intratumoral Fibrosis.Cancer science · 2026Article
- Saffron andWorld journal of gastroenterology · 2025Article
- [Two-sample Mendelian randomization analysis for the causal relationship between 91 circulating inflammatory proteins and liver cirrhosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- Biochemical and Molecular Studies on the Role of Celecoxib and Some Related Bipyrazoles in Mitigating Induced Liver Injury in Experimental Animals.Drug design, development and therapy · 2025Article
- Cytoglobin suppresses oxidative damage and compensatory proliferation via inhibiting AKT/ERK1/2/CyclinD1 axis in hepatocellular carcinoma.American journal of cancer research · 2025Article
- Article
- Impact of Liver Fibrosis Severity on Oncological Prognosis in Hepatocellular Carcinoma.Liver cancer · 2024Article
- cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation.Cell communication and signaling : CCS · 2024Review
- BMP7-Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorate Liver Fibrosis by Targeting Activated Hepatic Stellate Cells.International journal of nanomedicine · 2024Article
- Insights into the function of cytoglobin.Biochemical Society transactions · 2023Review
- Nitric Oxide Derived from Cytoglobin-Deficient Hepatic Stellate Cells Causes Suppression of CytochromeAntioxidants & redox signaling · 2023Article
- Nanodrug rescues liver fibrosis via synergistic therapy with HCommunications biology · 2023Article
- Erratum.Hepatology (Baltimore, Md.) · 2022Article
- Diabetes Mellitus May Exacerbate Liver Injury in Patients with COVID-19: A Single-Center, Observational, Retrospective Study.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2022Article
- The m6A reader YTHDF3-mediated PRDX3 translation alleviates liver fibrosis.Redox biology · 2022Article
- Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species.Oncogenesis · 2022Article
- Efficacy and safety of fenofibrate add-on therapy in patients with primary biliary cholangitis refractory to ursodeoxycholic acid: A retrospective study and updated meta-analysis.Frontiers in pharmacology · 2022Article
- Novel Therapeutic Targets in Liver Fibrosis.Frontiers in molecular biosciences · 2021Review
Corrections and comments
- Erratum issuedErratum.2022
Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsAntifibrotic therapy remains an unmet medical need in human chronic liver disease. We report the antifibrotic properties of cytoglobin (CYGB), a respiratory protein expressed in hepatic stellate cells (HSCs), the main cell type involved in liver fibrosis. APPROACH AND
resultsCygb-deficient mice that had bile duct ligation-induced liver cholestasis or choline-deficient amino acid-defined diet-induced steatohepatitis significantly exacerbated liver damage, fibrosis, and reactive oxygen species (ROS) formation. All of these manifestations were attenuated in Cygb-overexpressing mice. We produced hexa histidine-tagged recombinant human CYGB (His-CYGB), traced its biodistribution, and assessed its function in HSCs or in mice with advanced liver cirrhosis using thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). In cultured HSCs, extracellular His-CYGB was endocytosed and accumulated in endosomes through a clathrin-mediated pathway. His-CYGB significantly impeded ROS formation spontaneously or in the presence of ROS inducers in HSCs, thus leading to the attenuation of collagen type 1 alpha 1 production and α-smooth muscle actin expression. Replacement the iron center of the heme group with cobalt nullified the effect of His-CYGB. In addition, His-CYGB induced interferon-β secretion by HSCs that partly contributed to its antifibrotic function. Momelotinib incompletely reversed the effect of His-CYGB. Intravenously injected His-CYGB markedly suppressed liver inflammation, fibrosis, and oxidative cell damage in mice administered TAA or DDC mice without adverse effects. RNA-sequencing analysis revealed the down-regulation of inflammation- and fibrosis-related genes and the up-regulation of antioxidant genes in both cell culture and liver tissues. The injected His-CYGB predominantly localized to HSCs but not to macrophages, suggesting specific targeting effects. His-CYGB exhibited no toxicity in chimeric mice with humanized livers.
conclusionsHis-CYGB could have antifibrotic clinical applications for human chronic liver diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.