ArticleLaboratory investigation; a journal of technical methods and pathology2014
Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver.
Article in Laboratory investigation; a journal of technical methods and pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
- RNA-binding protein LARP6 coordinates hepatic stellate cell activation and liver fibrosis.The Journal of clinical investigation · 2026Article
- Therapeutic Potential of Cytoglobin and Neuroglobin in Oxidative Stress-Driven Liver Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Fibulin-2 Facilitates Malignant Progression of Hepatocellular Carcinoma.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species.Oncogenesis · 2022Article
- Inhibition of Hepatic Stellate Cell Activation Suppresses Tumorigenicity of Hepatocellular Carcinoma in Mice.The American journal of pathology · 2021Article
- Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity.JHEP reports : innovation in hepatology · 2021Article
- Hexa Histidine-Tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species.Hepatology (Baltimore, Md.) · 2021Article
- The Tumor Microenvironment in Liver Metastases from Colorectal Carcinoma in the Context of the Histologic Growth Patterns.International journal of molecular sciences · 2021Review
- Comprehensive analysis of liver and blood miRNA in precancerous conditions.Scientific reports · 2020Article
- Cytoglobin-expressing cells in the splenic cords contribute to splenic fibrosis in cirrhotic patients.Histology and histopathology · 2020Article
- Role of cytoglobin, a novel radical scavenger, in stellate cell activation and hepatic fibrosis.Clinical and molecular hepatology · 2020Review
- The Hepatic Sinusoid in Aging and Disease: Update and Advances From the 20th Liver Sinusoid Meeting.Hepatology communications · 2020Article
- Human Liver-Derived Extracellular Matrix for the Culture of Distinct Human Primary Liver Cells.Cells · 2020Article
- Programmed death-ligand 1 expression is an unfavorable prognostic factor of hepatocellular carcinoma after archiving sustained virologic response for hepatitis C virus infection.Oncology letters · 2019Article
- Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice.Scientific reports · 2018Article
- Epalrestat Stimulated Oxidative Stress, Inflammation, and Fibrogenesis in Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications.Genes · 2018Article
- Stagnation of histopathological improvement is a predictor of hepatocellular carcinoma development after hepatitis C virus eradication.PloS one · 2018Observational
- Development of a peptide-modified siRNA nanocomplex for hepatic stellate cells.Nanomedicine : nanotechnology, biology, and medicine · 2018Article
- Human hepatic stellate cell isolation and characterization.Journal of gastroenterology · 2018Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytoglobin (CYGB) is ubiquitously expressed in the cytoplasm of fibroblastic cells in many organs, including hepatic stellate cells. As yet, there is no specific marker with which to distinguish stellate cells from myofibroblasts in the human liver. To investigate whether CYGB can be utilized to distinguish hepatic stellate cells from myofibroblasts in normal and fibrotic human liver, human liver tissues damaged by infection with hepatitis C virus (HCV) and at different stages of fibrosis were obtained by liver biopsy. Immunohistochemistry was performed on histological sections of liver tissues using antibodies against CYGB, cellular retinol-binding protein-1 (CRBP-1), α-smooth muscle actin (α-SMA), thymocyte differentiation antigen 1 (Thy-1), and fibulin-2 (FBLN2). CYGB- and CRBP-1-positive cells were counted around fibrotic portal tracts in histological sections of the samples. The expression of several of the proteins listed above was examined in cultured mouse stellate cells. Quiescent stellate cells, but not portal myofibroblasts, expressed both CYGB and CRBP-1 in normal livers. In fibrotic and cirrhotic livers, stellate cells expressed both CYGB and α-SMA, whereas myofibroblasts around the portal vein expressed α-SMA, Thy-1, and FBLN2, but not CYGB. Development of the fibrotic stage was positively correlated with increases in Sirius red-stained, α-SMA-positive, and Thy-1-positive areas, whereas the number of CYGB- and CRBP-1-positive cells decreased with fibrosis development. Primary cultured mouse stellate cells expressed cytoplasmic CYGB at day 1, whereas they began to express α-SMA at the cellular margins at day 4. Thy-1 was undetectable throughout the culture period. In human liver tissues, quiescent stellate cells are CYGB positive. When activated, they also become α-SMA positive; however, they are negative for Thy-1 and FBLN2. Thus, CYGB is a useful marker with which to distinguish stellate cells from portal myofibroblasts in the damaged human liver.
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